Background. Non-invasive prenatal testing (NIPT) analyses the cell-free fetal DNA (cffDNA) present in maternal plasma. It is used for the screening of autosomal trisomies and sex chromosome aneuploidies (SCAs). Objectives. Compare the positive predictive value (PPV) of a high-risk cffDNA test result for SCAs (Monosomy X, 47,XXX, 47,XXY and 47,XYY) and autosomal trisomies (T21, T18 and T13) with confirmatory diagnostic tests in singleton pregnancies. Identify the main reason for discordant and inconclusive results. Search strategy. PubMed, Web of Science and Scopus from 2017. Selection criteria. Primary research articles on cffDNA testing of autosomal trisomies and SCAs in singleton pregnancies. Data collection and analysis. The methodological characteristics of the studies and the statistical results of each aneuploidy were collected. The risk of bias was assessed using the CASP tool. Main results. A total of 14 studies were included. Amongst the autosomal trisomies, T21 had the highest PPVs, whereas T13 showed the lowest PPVs. As for the SCAs, the lowest PPVs were found with Monosomy X. Although discordant and inconclusive results were not rigorously reported, mosaicism was the main cause of false positives and an insufficient cffDNA fraction was the main reason for inconclusive results. Conclusions. CffDNA is a reliable screening tool for the common autosomal trisomies, and it is also useful for prenatal screening of SCAs, although the PPVs are lower. A positive NIPT result should be followed with a confirmatory test. Funding. The review was carried out with no funding. Keywords. Cell-free fetal DNA, non-invasive prenatal testing, aneuploidy, trisomy.

Aim: To develop evidence-based clinical algorithms for the assessment and management of spontaneous, uncomplicated labour and vaginal birth. Population: Pregnant women at any stage of labour, with singleton, term pregnancies considered to be at low risk of developing complications. Setting: Health facilities in low- and middle-income countries. Search Strategy: We searched for relevant published algorithms, guidelines, systematic reviews and primary research studies on Cochrane Library, PubMed, and Google on terms related to spontaneous, uncomplicated labour and childbirth up to 01 June 2023. Case scenarios: Three case scenarios were developed to cover assessments and management for spontaneous, uncomplicated first, second and third stage of labour. The algorithms provide pathways for definition, assessments, diagnosis, and links to other algorithms in this series for management of complications. Conclusions: We have developed three clinical algorithms to support evidence-based decision making during spontaneous, uncomplicated labour and vaginal birth. These algorithms might help guide health care staff to institute respectful care, appropriate interventions where needed, and potentially reduce the unnecessary use of interventions during labour and childbirth.

Aim: Since the efficacy of some tricyclic antidepressants (TCAs) in reducing pain has been reported, several studies have evaluated the analgesic potency of other drugs in this category. This study aims to accumulate all the data evaluating the efficacy of nortriptyline in reducing pain. Methods: In accordance with the PRISMA guideline, clinical trials were imported from PubMed, Web of Science, and Scopus (until February 2023). Screening stages (based on pre-defined eligibility criteria) and data extraction were conducted by two independent researchers. Random- and fixed-effect meta-analysis was performed to pool the data. Publication bias and study heterogeneity were assessed. The Cochrane Collaboration tool was utilized to determine the risk of bias, and the certainty of outcomes was evaluated by the Grade criteria. Results: Of the initial 648 studies, 14 were finally imported. Except for one study, all other studies reported that nortriptyline significantly reduces various types of pain. The pooled standardized mean difference (95% CI) of reducing pain score as pre- and post-treatment, compared with placebo, and compared with other alternative analgesics were -1.20 [-1.48, -0.93], 0.43 [0.23, 0.64], and -0.18 [-0.39, 0.03], respectively. While the most reported side effects were dry mouth and constipation, all studies reported that side effects were not serious and were well tolerated. Outcomes for the effectiveness of nortriptyline and its tolerability got high certainties. Some studies reported the equality of nortriptyline with amitriptyline and gabapentin in terms of their analgesic effects. Conclusion: Using nortriptyline as an analgesic is effective while being safe and well-tolerated.

Background: Crimean-Congo hemorrhagic fever (CCHF) is a severe viral illness with high mortality rates. Nosocomial transmission poses a significant risk to healthcare workers (HCWs). Materials/methods: In this study, we evaluated the effectiveness of ribavirin in post-exposure prophylaxis (PEP) among HCWs with high-risk contacts. Exposures are grouped into 3 categories. The high-risk group consisted of HCWs who were directly exposed to blood or bodily fluids. We also included HCWs who participated in CPR without wearing appropriate PPE to the high-risk group. The moderate-risk group consisted of HCWs without a visible exposure to blood or bodily fluids but handled patient without appropriate PPE. Results: At least 38 HCWs had contact with the index fatal patient. None of the HCWs who had contact with the patient had appropriate PPE. Patient’s PCR and IgM were positive for CCHF. Among all known contacts, all HCWs in high and moderate risk groups (n:24) received PEP with ribavirin. No moderate or severe side effects were observed due to ribavirin. None of the HCWs developed nosocomial CCHF. Conclusions: There are still life-threatening gaps in the compliance of the HCWs to standard precautions. Ribavirin seems an effective and well tolerated agent for PEP of nosocomial CCHF.

Adolescents are the primary cohort for routine human papillomavirus (HPV) vaccination, but unvaccinated adults may also benefit. A lack of consensus on which adults to target and the presence of reimbursement barriers likely contribute to the lag in adult vaccinations, highlighting missed prevention opportunities. Understanding factors contributing to risk of HPV infection and disease could help in decision making on vaccination at an individual level. This review summarizes existing literature on risk factors for HPV infection and disease and includes 153 studies reporting relative risks or odds ratios for factors associated with HPV infection or disease in adults, published between 2009 and 2020. Despite inconsistent design and reporting of risk factors across studies, this review confirmed several risk factors associated with adult infection, including HIV positivity, number of sex partners, and smoking. These findings can support policymaking, guideline development, and clinical decision making for HPV vaccination and screening of high-risk adult groups.

Over the last two decades, lipid nanoparticles (LNPs) have evolved as an effective biocompatible and biodegradable RNA delivery platform in the field of nanomedicine, biotechnology and drug delivery, with the current successes as COVID-19 mRNA vaccines. Therefore, it is important to provide a general workflow of studying RNA-based LNP performance, which further offers useful guidance for researchers who want to work in the RNA-based LNP field. In this perspective, we first summarized the approaches for the preparation of LNPs, followed by the introduction of the key characterization parameters. Then, the in vitro evaluation of LNP performance including cell selection, cell viability, cellular association/uptake, endosomal escape and their efficacy was summarized. Finally, the in vivo assessment in the aspects of animal selection, administration, dosing and safety, and their therapeutic efficacy was discussed. We hope this perspective can offer valuable guidance to researchers who enter the field of RNA-based LNPs and help them understand the crucial parameters that RNA-based LNP demands.

The river morphology of a braided-type river is rather complex. High sediment transport rates and frequently changing discharges are the cause of dynamic planform evolution. Over the past few decades, scientific attention has been directed toward understanding the coexistence of alternating bars and the consequent emergence of confluences and divergences, all of which interact intricately with the process of bank erosion. It is still rather challenging to estimate or predict the total sediment transport rate in such type of rivers, especially by considering various hydrologic data and climate effects. This study is focused on a reach of the Devoll River in Albania, located upstream of the Banja dam. Understanding the morphodynamic of this river reach holds significance due to the expanding delta upstream of the dam reservoir. The objectives of the two-dimensional (2D) depth-averaged approach of the present study are to investigate the temporal variation of braided intensity of Devoll River due to using a discharge hydrograph from hydrologic data compared to the regulated one from the upstream dam on the morphodynamic of the river, and estimate the sediment transport rate of this complex braided river. After evaluating various parameters such as 11 different sediment transport functions, the best results were reached for a cell size of 5×5 m 2, Manning roughness coefficient of 0.03, Meyer-Peter and Müller’s sediment function, Hayashi et al. (1980) hiding function, and Van Rijn bed roughness predictor in this study. In addition, the results of comparing satellite images and modeling the river from 2019 to 2023 show that the braided index (BI) decreased, and this can be due to the fact that the real scenario of the river has a regulated discharge (scenario A) compared to the non-regulated discharge of hydrologic data (scenario B), in the mentioned period. Moreover, the study also estimates sediment transport rates, with scenario A showing higher values for total bed load rate (35.93 kg/s/m) and suspended load concentration (652.48 mg/l) compared to scenario B (16.32 kg/s/m and 152.39 mg/l). This research highlights the impact of regulated discharge on sediment transport in a complex braided river.

With the gradual development of the restoration and protection of the water ecosystem, the research and safegard of ecological flow have received much attention. However, there is a lack of systematization of the literature in the field of “ecological flow” and a lack of in-depth understanding of the main and topical contents of the research in this field. In order to gain an in-depth understanding of the progress and current status of research on ecological flows, this paper searched Web of Science core databases for scientific papers published from 1999 to 2021 on the topic of “ecological flow”. The retrieved 18,128 research papers on ecological flows were also visualized and analyzed by using CiteSpace software for documents per year, category, country and institution distribution, co-citation, and clustering. The results show that research papers on ecological flows have shown an increasing trend since 1999. The categories of disciplines involved cover a wide range of disciplines such as environmental science and ecology, water resources, and so on. The United States ranks first in the number of publications and has a high influence. A total of five clusters were obtained through keywords clustering, with more overlapping areas, hydrological modeling, and aquatic ecosystems are the mainstream of research in the field of ecological flow. “Ecological flow” is still in a phase of rapid development, with the depth of research gradually increasing and the breadth of research expanding. In a long time, the keywords “r package”, “ecological flow”, “loess plateau”, “yellow river” and “emission” will be the center of the field of “ecological flow”.

We quantified temporal dynamics of wood storage, input, and transport in a third-order stream over a 23-year period in adjacent old-growth and second-growth forested reaches in the Cascade Mountains of Oregon. Numbers and volumes of large wood (i.e., standing stock) in the old growth reach were more than double and triple, respectively, than those in the second growth. Annual inputs of large wood were highly variable. Wood numbers delivered into the old-growth reach were 3X higher and wood volume 10X greater than that of the second growth. Movement of number and volume of logs did not differ significantly between the two reaches. Less than 3% of the logs moved in most years, and the highest proportion moved in the year of the 1996 flood (9% in old growth and 17% in second growth). The majority of wood occurred in accumulations (i.e., jams) in both reaches. The second-growth reach lacked major jams, but 29% of the logs in the old growth were in full-channel spanning jams. Long-term observations of annual storage, input, and movement best reveal the dynamics of wood rather than static representations of the characteristics of wood. Input events and transport of wood in Mack Creek were episodic and varied greatly over the 23-yr study, which illustrates one of the major challenges and opportunities for understanding the cumulative dynamics of wood in streams.

Since a single miRNA may control many target genes across several pathways in a cell, it is clear that miRNAs are very potent genetic regulators. Because of this characteristic, miRNAs are promising therapeutic agents for reversing the altered cellular processes that characterize disease phenotypes. MiRNAs' strength is in their ability to regulate a wide variety of cellular processes, but this also makes them vulnerable to off-target effects. In this review, we highlight the primary obstacles and provide approaches to resolving these issues in order to advance miRNA therapeutics. Methods that have advanced to clinical trials are highlighted in particular. What potential do medicinal uses of miRNA hold? The function of microRNAs (miRNAs; see Glossary) is to regulate the expression of proteins after their transcription. throughout 2300 unique miRNAs have been identified in human cells [1, 2, 3]. Their levels of expression vary throughout time and across various types of tissue. Box 1 provides key information on the biosynthesis and function of miRNAs. The following discussion focuses on miRNA fidelity criteria. MicroRNA biogenesis in cells. Sequences encoding microRNAs may be found in the intronic sections of protein-coding genes, the exonic regions, or the intergenic regions. They might be under the control of their host genes' promoters or have their own [103]. Primary miRNAs (pri-miRNAs) are transcribed from miRNA encoding sequences by RNA polymerase II or III into mature miRNAs (miRNAs), which may be several thousand nucleotides in length and have a hairpin structure (the biogenesis of miRNAs has been extensively discussed elsewhere; see, for example, [103., 104., 105.]). The Drosha-DGCR8 microprocessor complex in the nucleus further processes pri-miRNAs to produce a miRNA precursor (pre-miRNA) of around 70 nucleotides in length. In a noncanonical biogenesis, intron-encoded pre-miRNAs (mirtrons) may be directly processed together with their coencoded transcripts by spliceosomes. Once in the cytoplasm, RNase Dicer and the double-stranded RNA binding enzyme TRBP break the pre-miRNA hairpin into a miRNA duplex of around 22 nucleotides in length. The RISC is then modified to contain single strands of miRNA, enabling the ribonucleoprotein complex to attach to specific sequences within the 3' untranslated regions of messenger RNAs. The seed region, typically located between nucleotides 2 and 7 at the 5' end of the miRNA, is where reverse complementary binding occurs. This binding prevents or halts the translation process. As miRNAs are thought to regulate as much as 60% of all protein-encoding genes post-transcriptionally [106], they are pivotal in cellular signaling and have far-reaching effects on almost every biological activity [6]. New data suggests that microRNAs (miRNAs) may go into the nucleus to affect gene transcription [107], expanding their influence on cellular signaling networks beyond their actions at the post-transcriptional level.

Disease conditions often include dysregulation of microRNAs (miRNAs), which are short noncoding RNAs with gene regulatory activities. MiRNAs are attractive biomarkers for the diagnosis and prediction of cancer and cardiovascular disorders because they are reasonably stable, readily quantified, and accessible from plasma or other bodily fluids. The third most frequent form of cardiovascular illness, venous thromboembolism (VTE) is associated with a high rate of morbidity and death globally. More evidence is emerging to support the concept that microRNAs (miRNAs) have a role in controlling the pathophysiology of VTE and serving as VTE biomarkers. Cancer patients have a higher incidence of venous thromboembolism (VTE) than the general population. However, existing risk prediction models for cancer-associated thrombosis (CAT) perform suboptimally, and innovative biomarkers are thus urgently required to determine which patients may benefit the most from thromboprophylaxis. The pathophysiology of VTE will be reviewed, beginning with the mechanistic role played by miRNAs. Then, miRNAs' potential as prognostic biomarkers for VTE in cancer-free people is discussed, and finally, CAT is the topic of extensive attention. Differential regulation of some of the CAT-associated miRNAs was also seen in VTE, providing more insight into CAT's pathogenesis. Our findings suggest that future research should use sufficiently powered methods to identify the miRNA panel that most accurately predicts VTE and CAT. To determine if miRNAs, either on their own or as part of established risk models, have promise as VTE and CAT biomarkers, validation studies employing similar patient groups are needed.

MicroRNAs (miRNAs) are a class of short, non-coding RNAs that play an important role in a wide range of biological processes by directly binding to and repressing the expression of certain target genes in a post-transcriptional manner. More than one-half of human genes were controlled by miRNAs and their abnormal expression was discovered in different human illnesses, including malignancies. In recent years, researchers have discovered mounting evidence that the recently discovered miRNA miRNA-338 has a role in the development of a wide variety of malignancies, including lung cancer, hepatocellular carcinoma, breast cancer, glioma, and others. Although a number of targets and signaling pathways such as MACC1 and Wnt/β-catenin signaling pathway were revealed to be controlled by miRNA-338, their roles in tumor growth are still vague and the underlying molecular processes are still uncertain. In this article, we summarized the current state of knowledge on miRNA-338 and its activities in various human cancers in the hopes that this would spark fresh ideas for future research and the development of targeted therapies.

This article explores the fundamental importance of implementing rapid tests in the diagnosis of dengue, emphasizing their essential role in early detection and efficient management of this mosquito-transmitted disease. These tests, based on the detection of viral antigens or specific antibodies, not only provide results in record time but also constitute a significant contribution to global healthcare. Rapid tests offer an immediate response, allowing timely medical intervention that can make a difference in the clinical course of the patient. Their ability to identify the virus in the early stages of infection is crucial, not only for individualized care but also for mitigating the spread of dengue at the community level. Moreover, by distinguishing between virus serotypes, these tests provide a more precise perspective for the application of therapeutic and preventive strategies. The accessibility and simplicity of rapid tests become key elements for their positive impact, especially in resource-limited settings. The swift availability of results not only accelerates clinical decision-making but also facilitates the collection of crucial epidemiological data. This information contributes to the strategic planning of public health authorities, enabling a coordinated and efficient response to dengue outbreaks and epidemics. The widespread adoption of rapid tests in dengue diagnosis emerges as a fundamental pillar in global healthcare. Their ability to provide rapid and accurate results, their role in early detection, and their contribution to efficient management make these tests an invaluable tool in the fight against this prevalent disease, redefining how we approach the diagnosis and treatment of dengue on a global scale.

Near ubiquitous reproductive trends across taxa follow a pattern in which output increases with latitudes and decreases with calendar date. Research grounded in life history theory provides separate ultimate explanations for latitudinal and seasonal trends. Here we frame these dual trends as a Simpson's paradox and attempt to gain insights into proximate cues that might account for both simultaneously. Using citizen science data on Eastern bluebirds, we found highest support for a model of clutch size based on change in day length at clutch initiation. Describing reproductive trends based on non-biologically relevant constructs of latitude and calendar date obscured links between proximate and ultimate explanations. For birds, our findings are consistent with an internal coincidence model of circadian rhythmicity as a proximate control of clutch size. Other avian studies might benefit from viewing clutch size as a circadian behavior of clutch initiation and termination rather than a quantified trait.

N 6-methyladenosine (m 6A) is a common messenger RNA (mRNA) modification that affects diverse physiological processes in stress responses. However, the role of m 6A modification in plants coping with herbivore stress remains unclear. Here we found that an infestation of brown planthopper (BPH) Nilaparvata lugens female adults enhanced the rice resistance to BPH. An m 6A methylome analysis of BPH-infested and un-infested rice samples were measured to explore the interaction between rice and BPH. m 6A methylation occurs mainly in genes actively expressed in rice following BPH infestation, while an analysis of the whole-genomic mRNA distribution of m 6A showed that BPH infestation caused an overall decrease in the number of m 6A methylation sites across the chromosomes. Genes involved in components of the m 6A modification machinery, BPH resistance, and several defense-related (such as JA, SA and cellulose) pathways were heavily methylated by m 6A in BPH-infested rice compared to those in un-infested rice. In contrast, m 6A modification levels of growth-related phytohormones (auxin and gibberellin) biosynthesis-related genes were significantly attenuated under BPH attack, accompanied by downregulated expression of these transcripts, indicating that rice growth was restricted during BPH attack to rapidly optimize resource allocation for plant defense. Integrative analysis of the differential patterns of m 6A methylation and the corresponding transcripts showed a positive correlation between m 6A methylation and transcriptional regulation. In conclusion, the process of m 6A modification acts as an important strategy for regulating expression of genes involved in rice defense and growth during rice-BPH interaction.

Underwater target localization technology plays a vital role in the development and utilization of marine resources. Due to the multipath effect in the hydroacoustic channel, the received signal is the superposition of a series of direct and reflected acoustic paths, making it challenging to accurately identify the direct path using existing methods. To address this issue, this paper proposes a high-precision direct path recognition method based on LightGBM, which utilizes the amplitude, Time of Arrival (TOA), reception angle, and phase of the received pulse as input features. Meanwhile, due to the propagation time of acoustic waves from transmitter to receiver cannot be linearly converted to a distance value, as in the case of radio ranging in air, a method based on Effective Sound Velocity (ESV) is introduced to compensate for the bending of sound rays. By utilizing the recognized direct path delay value and the sound velocity value after compensating for sound ray bending, we can calculate the precise position of underwater targets. Experimental results validate the effectiveness of the proposed method in significantly improving the accuracy of underwater target localization.

Membrane proteins are those biomolecules that are attached to or incorporated into the membranes of cells and their organelles. Depending on their functions, they are located in various regions of a cell and are essential to several cellular processes. The locale revelation of these biomolecules is critical as it portrays their activities. Most protein subcellular localization predictors have been trained particularly on globular type and perform poorly on those residing on membranes, specifically through Deep Learning. To overcome this issue, membrane proteins are forecasted in three distinct locations, (a) plasma membrane, (b) internal membrane, and (c) organelle membrane. Features are extracted through Pseudo Amino Acid Composition and some other features from a redundancy curtailed MemLoci dataset. Pseudo Amino Acid Composition is an illustrious approach that excerpts factual protein information through amino acid sequences. Another key feature is that the Pseudo Amino Acid Composition’s impact is unrelated to the Deep Learning Execution of these membrane proteins. This novel study employs four deep learning models, including (a) Artificial Neural Networks (ANN), (b) Recurrent neural networks (RNN), (c) Convolutional neural networks (CNN), and (c) Long Short Term Memory (LSTM). After extensive experimentation, the accuracy of yields is 83.2%, 83.4%, 82.4%., and 80.5% respectively. The outcomes indicate that the simple RNN and ANN models, which are less used in the research, are more suitable compared to the other two models CNN and LSTM which are frequently implemented models in proteomics. The results of the first two models is approximately similar, with a difference of 0.2% among each other, however, they surpass the other two models with better of outcomes in the range of 2 - 3%.

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by the formation of extracellular amyloid- β (A β) plaques. The underlying cause of AD is unknown, however, post-translational modifications (PTMs) of A β have been found in AD patients and are thought to play a role in protein aggregation. One such PTM is pyroglutamylation, which can occur at two sites in A β, Glu3 and Glu11. This modification of A β involves the truncation and charge-neutralization of N-terminal glutamate, causing A β to become more hy- drophobic and prone to aggregation. The molecular mech- anism by which the introduction of pyroglutamate (pE) pro- motes aggregation has not been determined. To gain a greater understanding of the role that charge neutralization and trun- cation of the N-terminus plays on A β conformational sam- pling, we used the Drude polarizable force field (FF) to per- form molecular dynamics simulations on A β pE3-42 and A β pE11-42 and comparing their properties to previous simulations of A β 1-42. The Drude polarizable FF allows for a more accurate representation of electrostatic interactions, therefore pro- viding novel insights into the role that charge plays in pro- tein dynamics. Here, we report the parametrization of pE in the Drude polarizable FF and the effect of pyroglutamyla- tion on A β. We found that A β pE3-42 and A β pE11-42 alter the permanent and induced dipoles of the peptide. Specifically, we found that A β pE3-42 and A β pE11-42 have modification- specific backbone and sidechain polarization response and perturbed solvation properties that shift the A β conforma- tional ensemble.

Objective of investigation: Enhancing soil organic carbon (SOC) content in farmland is crucial for soil quality maintenance and food security. Crop rotation plays a significant role in this regard. However, the relationship between crop rotation and SOC sequestration remains unclear. This study focused on the effects of wheat −maize crop rotation on SOC in the Sushui River Basin in 2017–2021. Experimental material: soil organic carbon (SOC) content of monoculture wheat (47), monoculture maize (30), and wheat-maize rotation (35) sites in 2017 and 2021 cropland quality monitoring sites. Influencing factors were average temperature and rainfall during the study period, topographic factors, soil factors, and anthropogenic factors dominated by cropping systems. Method of investigation: Geographically Weighted Regression and Geodetector were used to explore the spatial effects of major food cropping systems on SOC trends and their interactions with other factors. Data collection: Soil, climate, and terrain data were obtained from Shanxi Province Cropland Quality Monitoring Data, Yuncheng Meteorological Bureau, and the Geospatial Data Cloud website of the Computer Network Information Center of the Chinese Academy of Sciences, respectively. Results: Analysis of variance (ANOVA) indicated significant differences only between wheat and maize monocrops. Altitude, temperature, rainfall, and pH were the main factors affecting SOC spatial heterogeneity. Although the impact of the cropping system alone on spatial heterogeneity was not significant, the influence increased after interactions with other factors. Concerning SOC variation, wheat–maize rotation had a trade-off effect with elevation and synergistic effects with rainfall and pH. It displayed a synergistic effect with temperature in the southwest and a trade-off effect in the northeast. Conclusions: The degrees of trade-offs and synergy varied spatially among all interacting factors. Our results provide valuable insights that could facilitate optimization of planting layout and improvement of farmland management schemes.

Rhino-orbital-cerebral mucormycosis (ROCM) is a rare angioinvasive fungal infection known to be associated with high morbidity and over 50% mortality and has increased lately due to increasing predisposing immunocompromising comorbidities as well as COVID-19. In addition to the common acute disease progression, chronic less aggressive courses have been described less often. In this paper we report two cases – a 75-year-old woman with diabetes and a 39-year-old man with recurrent diabetic ketoacidosis. Both presented initially with acute sinonasal symptoms, were positive for SARS-COV-2 and later diagnosed with acute ROCM.  Both underwent mutilating surgical therapy as well as high administered dose Amphotericin B and long term continuous antifungal therapy. Patient 1 showed stable symptoms with radiographically increasing disease and died of urosepsis 5 months after first surgery. Patient 2 was first lost to follow-up after repatriation to his home country and 1 year later sent us a holiday picture of himself, having recovered from the disease.Key words:Rhino-orbital-cerebral mucormycosis, mucormycosis, Amphotericin-B, COVID-19, invasive fungal infection

Background and Aims: The long-term respiratory sequelae of COVID-19 infection in children remain poorly understood and may differ across countries. This study aims to investigate the respiratory sequelae, including residual respiratory symptoms and pulmonary function in Thai children. The secondary aim is to identify factors associated with the respiratory sequelae. Materials and Methods: This is an observational study involving 56 healthy children, aged between 7-18 years, who were diagnosed with COVID-19 infection from July 2021 to February 2023. Clinical data relating to COVID-19 infection and persistent symptoms after the infection were assessed after the infection up to six months. Spirometry was performed to assess pulmonary function. Results: Post COVID-19 symptoms were identified in 14 patients (25%), with fatigue, cough, and dyspnea being common symptoms (28-35%). A significant correlation was found between post COVID-19 symptoms and pneumonia (OR = 6.00, 95%CI [1.54,23.33], p=0.01). Abnormal pulmonary function was identified in 10 patients (17.8%) with obstructive impairment being the most common. However, there were no significant association between clinical factors and pulmonary function impairment. Conclusion: Prolonged respiratory symptoms and abnormal pulmonary function following COVID-19 infection are not uncommon in children. The post COVID-19 symptoms are possibly associated with COVID-19 pneumonia.

Comparing causal effect estimates obtained using observational data to those obtained from the gold standard (i.e., randomized controlled trials, RCTs) helps us assess the validity of these estimates. However, comparisons are challenging due to differences between observational data and RCT generated data: First, the treatment assignment mechanism is often unknown for observational data, and second, the sampling mechanism often differs between the RCT and the observational data. Differences in the treatment assignment mechanism introduce potential confounding, whereas differences in the sampling mechanism introduce sampling bias. This article proposes a two-step framework for the validation of causal effect estimates obtained from observational data by adjusting for both mechanisms. A simulation study is conducted to show that our suggested two-step framework enables observational data to produce causal effect estimates similar to those of an RCT. An application of our approach to validate treatment effects of adjuvant chemotherapy obtained from registry data is demonstrated. This article establishes a novel framework for comparing causal effect estimates between observational data and RCT data, facilitating the assessment of the validity of causal effect estimates obtained from observational data.

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This study aims to evaluate the acupuncture effect on exercise-induced fatigue utilizing transcranial magnetic stimulation (TMS). A total of 20 sports enthusiasts were recruited in this study, all participants would be assigned to receive acupuncture and sham acupuncture intervention on exercise-induced fatigue randomly. TMS and heart rate monitor would be used to measure the amplitude and latency of motor evoked potential (MEP) and heart rate every 5 minutes over a 30-minute period. Lactate Scout+ was used to measure the blood lactic acid (BLA) in baseline, 0 minutes and 30 minutes after fatigue. Two-way repeated measures ANOVA was used to compare the difference between acupuncture method and time effects. Bonferroni post hoc tests were conducted to compare specific differences. Significance was set at P < 0.05. Interaction effect was found between acupuncture method and time effect in amplitude (F (1, 38) = 5.40, P < 0.001, η2 = 0.12) and latency (F (1, 38) = 3.78, P = 0.008, η2 = 0.09) of MEP. Acupuncture intervention can promote the recovery of heart rate especially at 30 minutes (P < 0.05), but which seem insufficient to generate significant difference in BLA (F (1, 38) = 0.067, P = 0.797, η2 = 0.002). Preliminary findings provide new perspectives for sports enthusiasts to relieve fatigue and reduce the inhibition of motor cortex excitability utilizing acupuncture.