bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological Changes Exacerbating the Spread of Invasive Ticks has Driven the Dispersal of Severe Fever with Thrombocytopenia Syndrome Virus Throughout Southeast Asia
Authors: Pérez Lester J , Baele Guy , Hong Samuel L , Cloherty Gavin A , Berg Michael G
Published: August 2024

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus recognized by the World Health Organization as an emerging infectious disease of growing concern. Utilizing phylodynamic and phylogeographic methods, we have reconstructed the origin and transmission patterns of SFTSV lineages and the roles demographic, ecological, and climatic factors have played in shaping its emergence and spread throughout Asia. Environmental changes and fluctuations in tick populations, exacerbated by the widespread use of pesticides, have contributed significantly to its geographic expansion. The increased adaptability of Lineage L2 strains to the Haemaphysalis longicornis vector has facilitated the dispersal of SFTSV through Southeast Asia. Increased surveillance and proactive measures are needed to prevent further spread to Australia, Indonesia, and North America.
Structural basis of AUC codon discrimination during translation initiation in yeast
Authors: Villamayor-Belinchón Laura , Sharma Prafful , Gordiyenko Yuliya , Llácer Jose L , Hussain Tanweer
Published: August 2024

In eukaryotic translation initiation, the 48S preinitiation complex (PIC) scans the 5′ untranslated region of mRNAs to search for the cognate start codon (AUG) with assistance from various eukaryotic initiation factors (eIFs). Cognate start codon recognition is precise, rejecting near-cognate codons with a single base difference. However, the structural basis of discrimination of near-cognate start codons was not known. We have captured multiple yeast 48S PICs with a near-cognate AUC codon at the P-site, revealing that the AUC codon induces instability in the codon-anticodon at the P-site, leading to a disordered N-terminal tail of eIF1A. Following eIF1 dissociation, the N-terminal domain of eIF5 fails to occupy the vacant eIF1 position, and eIF2β becomes flexible. Consequently, 48S with an AUC codon is less favourable for initiation. Furthermore, we observe hitherto unreported metastable states of the eIF2-GTP-Met-tRNAMet ternary complex, where the eIF2β helix-turn-helix domain may facilitate eIF5 association by preventing eIF1 rebinding to 48S PIC. Finally, a swivelled head conformation of 48S PIC appears crucial for discriminating incorrect and selection of the correct codon-anticodon pair during translation initiation.
Placental lesions in systemic lupus erythematosus pregnancies associated with small for gestational age infants
Authors: Dhital Rashmi , Jacobs Marni , Smith Chelsey J F , Parast Mana M
Published: August 2024

Objectives

Up to a quarter of pregnant individuals with SLE have small for gestational age (SGA) infants. We aimed to characterize placental pathology associated with SGA infants in SLE.

Methods

We retrospectively analysed SLE deliveries with placental analysis at UCSD from November 2018 to October 2023, comparing SLE pregnancies resulting in SGA to those that did not, and additionally, to matched pregnancies with SGA but without SLE.

Results

Placental analysis was available only for 28/70 (40%) SLE deliveries, which had high rates of adverse outcomes (75%). All exhibited at least one histopathologic abnormality. Key findings distinguishing 12 SLE placentas resulting in SGA infants (vs.16 without) included small placental disc for gestational age (100% vs 56%, P = 0.01), placental disc infarct (50% vs 6%, P = 0.02) and increased perivillous fibrin deposition (PVFD, 58% vs 0%, P = 0.001). All seven SLE placentas with increased PVFD resulted in SGA infants. Compared with matched non-SLE pregnancies with SGA (n = 36), the only distinguishing placental lesion was a higher prevalence of increased PVFD in SLE-associated SGA (58% vs 22%, P = 0.03).

Conclusion

The higher prevalence of increased PVFD in placentas of SLE-associated SGA may indicate a specific mechanism of placental injury leading to SGA in this context. Thus, its presence, particularly in context of SGA, should prompt providers to screen for an underlying autoimmune disease, including SLE. Systematic placental examination in context of SLE and associated autoimmune diseases could help evaluate responses to existing therapies, comparative studies of novel therapies and correlation to adverse outcomes.
Describing the Landscape of Medical Education Preprints on MedRxiv: Current Trends and Future Recommendations
Authors: Maggio Lauren A. , Costello Joseph A. , Artino Anthony R.
Published: August 2024

Purpose

A preprint is a version of a research manuscript posted to a preprint server prior to peer review. Preprints enable authors to quickly and openly share research, afford opportunities for expedient feedback, and enable immediate listing of research on grant and promotion applications. In medical education, most journals welcome preprints, which suggests that preprints play a role in the field’s discourse. Yet, little is known about medical education preprints, including author characteristics, preprint use, and ultimate publication status. This study provides an overview of preprints in medical education to better understand their role in the field’s discourse.

Method

The authors queried medRxiv, a preprint repository, to identify preprints categorized as “medical education” and downloaded related metadata. CrossRef was queried to gather information on preprints later published in journals. Data were analyzed using descriptive statistics.

Results

Between 2019 and 2022, 204 preprints were classified in medRxiv as “medical education,” with most deposited in 2021 (n = 76; 37.3%). On average, preprint full-texts were downloaded 1,875.2 times, and all were promoted on social media. Preprints were authored, on average, by 5.9 authors. Corresponding authors were based in 41 countries, with 45.6% in the United States, the United Kingdom, and Canada. Almost half (n = 101; 49.5%) became published articles in predominantly peer-reviewed journals. Preprints appeared in 65 peer-reviewed journals, with BMC Medical Education (n = 9; 8.9%) most represented.

Conclusions

Medical education research is being deposited as preprints, which are promoted, heavily accessed, and subsequently published in peer-reviewed journals, including medical education journals. Considering the benefits of preprints and the slowness of medical education publishing, it is likely that preprint depositing will increase and preprints will be integrated into the field’s discourse. The authors propose next steps to facilitate responsible and effective creation and use of preprints.
Treatment of interstitial lung disease in systemic sclerosis: guidelines and new clinical trial results
Authors: Johnson Sindhu R. , Bernstein Elana J.
Published: August 2024

Purpose of review

Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). The American College of Rheumatology (ACR), in conjunction with the American College of Chest Physicians (CHEST), recently published clinical practice guidelines for the treatment of adults with systemic autoimmune rheumatic disease-associated ILD, including SSc-ILD. Herein, we summarize evidence from randomized trials evaluating the safety and efficacy of pharmacologic therapies for the treatment of SSc-ILD.

Recent findings

In this review, we present findings from recent randomized controlled trials in SSc-ILD. The pharmacologic therapies discussed include immunosuppressive medications (mycophenolate, cyclophosphamide, rituximab, and tocilizumab) and antifibrotic medications (nintedanib and pirfenidone).

Randomized trials provide an evidence base for the SSc-ILD treatment recommendations put forth in the ACR/CHEST Guidelines for the treatment of ILD in people with systemic autoimmune rheumatic diseases. These guidelines will help inform clinical practice and highlight areas in which further research is needed.
Colchicine Prevents Post-Ablation Atrial Fibrillation Recurrence: A Systematic Review and Meta-Analysis
Authors: Jain Hritvik , Odat Ramez M. , Dey Debankur , Singh Jagjot , Kaur Ramanjot , Jain Jyoti , Goyal Aman , Ahmed Mushood , Marsool Mohammed Dheyaa Marsool , Passey Siddhant , Gole Shrey
Published: August 2024

Catheter ablation for atrial fibrillation (AF) is a commonly performed procedure, however, post-ablation AF recurrence is often observed due to inflammation and oxidative stress. Colchicine is a potent anti-inflammatory agent with conflicting efficacy in preventing post-ablation AF recurrence. A comprehensive literature search of the major bibliographic databases was conducted to retrieve studies comparing colchicine use versus placebo in AF patients post-ablation. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using the DerSimonian-Laird random-effects model. Statistical significance was set atP< 0.05. Six studies were included with 1791 patients (721 in the colchicine group and 1070 in the placebo group). Patients who received colchicine had significantly lower odds of AF recurrence on follow-up (OR, 0.62; 95% CI, 0.48–0.79;P= 0.0001) but had higher gastrointestinal side effects (OR, 2.67; 95% CI, 1.00–7.12;P= 0.05). There were no statistically significant differences in acute pericarditis (OR, 0.54; 95% CI, 0.27–1.05;P= 0.07) or hospitalization (OR, 1.03; 95% CI, 0.73–1.45;P= 0.87). Prophylactic use of colchicine after catheter ablation in patients with AF leads to a reduction in AF recurrence, albeit with increased gastrointestinal side effects. Colchicine use did not lead to a reduction in the rates of pericarditis and hospitalization after ablation. Large randomized controlled trials are necessary to evaluate the efficacy of colchicine in preventing AF recurrence, particularly focusing on the dose and duration of treatment to optimize the side effect profile.
The Use of the Pedicled Nonislanded Foot Fillet Flap to Avoid an Above-the-Knee Amputation after Trauma
Authors: Xiao Connie , Gebremariam Nebiyou Ermias , Nthumba Peter
Published: August 2024

Background:

Lower extremity trauma can have a devastating effect on the quality of the life of patients. To avoid limb amputation and its associated social stigma, many patients spend years undergoing multiple costly procedures, with prolonged hospital stays, all the while hoping for an elusive limb salvage. People with lower limb amputation experience higher energy requirements for walking, reduced aerobic capacity, and slower walking speeds, when compared with people with normal limbs. A below-knee amputation (BKA) is functionally superior to an above-knee amputation.

Methods:

Between 2012 and 2023, five patients underwent BKAs with a nonislanded foot fillet flap reconstruction of the BKA stump. Four of these patients had undergone previous multiple procedures in attempts at limb salvage. While two patients had sustained recent trauma, three were operated on electively.

Results:

All the BKA stumps healed without any complications. Only one patient complained of phantom limb pain. One patient will require the reconstruction of a lateral knee collateral ligament.

Conclusions:

This case series demonstrates the versatility of the pedicled foot fillet flap in addressing the different complications of lower extremity injury that may result in an unusable limb. The utility of this technique is especially valuable in low-resource settings where the built environment may be unfriendly to nonbipedal ambulation, and an urgent need for a return to economic productivity. Because prostheses are fairly accessible in Kenya, return to ambulation and economic productivity are anticipated following a BKA.
Implementation of In-house Computer-aided Design and Manufacturing for Accelerated Free Fibula Flap Reconstruction of Mandibular Defects in Cancer Patients
Authors: Lindhardt Joakim L. , Kiil Birgitte J. , Jakobsen Anders M. , Buhl Jytte , Krag Andreas E.
Published: August 2024

Background:

Computer-aided design and manufacturing (CAD/CAM) is widely adopted for optimizing microsurgical reconstruction of mandibular defects. However, commercial solutions are hampered by costs and lengthy lead times, with the latter being problematic in cancer surgery. This study aimed to investigate the efficiency of an in-house CAD/CAM service for expeditious planning and execution of free fibula mandibular reconstruction in head and neck cancer patients.

Methods:

This retrospective cohort study compared cancer patients undergoing segmental mandibulectomy and immediate free fibula flap reconstruction treated before and after implementation of in-house CAD/CAM. The primary endpoint was treatment delay from preoperative consultation to surgery. Cases in the two groups were matched on the number of fibula segments required for mandibular reconstruction. The control group underwent segmental mandibulectomy and fibula flap reconstruction by “freehand.” The CAD/CAM group underwent preoperative virtual surgical planning and CAD/CAM of intraoperative cutting guides for the mandibulectomy and fibula osteotomies. Outcomes were compared with the unpaired t test or Wilcoxon rank-sum test.

Results:

Sixteen patients were included in both groups. Treatment delay did not increase after implementation of in-house CAD/CAM with a median 6 (range 6–20) days wait in the CAD/CAM group and 8 (6–20) days wait in the control group (P = 0.48). Utilization of CAD/CAM significantly reduced fibula flap ischemia time with a mean of 18.4 [95% confidence interval 2.8; 33.9] minutes (P = 0.022).

Conclusions:

In-house CAD/CAM was implemented for free fibula flap mandibular reconstruction in head and neck cancer patients without causing treatment delay. Furthermore, CAD/CAM reduced fibula flap ischemia time.
Evidence-based research of the indicator system for evaluating the application effect of TCM standards
Authors: Bai Zhenggang , Zhu Yumeng , Shi Nannan
Published: August 2024

The traditional Chinese medicine evaluation indicator system can effectively identify and recognize deficiencies in the implementation of standards and provide a rationale for improving the technical content, enhancing the effectiveness of implementation and promoting the dissemination of traditional Chinese medicine culture and technology globally. Evidence-based principles can be an important method to guide the development of traditional Chinese medicine indicators and to promote the application of standards. This paper introduces the development status of NICE indicators and provides reference ideas for constructing evaluation indicators for traditional Chinese medicine standards application based on evidence-based principles. The specific steps for constructing an evaluation indicator system for traditional Chinese medicine standard application include identifying indicator domains, evidence synthesis, developing indicators, constructing an indicator system, cost-effectiveness and resource impact analyses, and finalizing indicators for training and promotion. To promote the further development of traditional Chinese medicine, it is necessary to strengthen the integrated construction of “guidelines-standards-indicators,” accelerate the establishment of a coordination mechanism between domestic and international organizations, and pay attention to the characteristics of traditional Chinese medicine and focus on implications for practice and policy.
Aortic stiffness: an age-related prognostic marker?
Authors: Torino Claudia , Lu Zuolin , Tilly Martijn J. , Ikram M. Kamran , Kavousi Maryam , Mattace-Raso Francesco
Published: August 2024

Aortic stiffness, a consequence of vascular aging, is an independent predictor of cardiovascular morbidity and mortality. However, the impact of age and sex on its predictive performance remains unclear. We have included 6046 individuals from the population-based Rotterdam study. Survival analyses were performed to investigate the impact of age and sex on the link between aortic stiffness and outcomes, including coronary heart disease (CHD), stroke, cardiovascular disease (CVD), cardiovascular and all-cause mortality. The added predictive value of aortic stiffness across age categories and by sex was assessed by using explained variation, Harrell's C index and Integrated Discrimination Improvement (IDI).

Aortic stiffness was independently associated with all outcomes [hazard ratio (95% confidence interval; CI): 1.16 (1.04–1.22) for CHD, 1.09 (1.00–1.19) for stroke, 1.11 (1.05–1.18) for CVD, 1.14 (1.05–1.23) for cardiovascular mortality, 1.08 (1.03–1.13) for all-cause mortality]. The strength of the association between aortic stiffness and stroke, cardiovascular and all-cause mortality decreased significantly by advancing age. The variance of the outcome (R
2) explained by aortic stiffness alone was noticeable in individuals younger than 60 years and negligible in the other age categories. The association of aortic stiffness and CHD was stronger in women than in men. Similarly, the difference in R
2 between women and men was greater for CHD than for the other considered outcomes. Our findings suggest that the gain in explained variation caused by aortic stiffness for CVD and mortality might be limited to individuals younger than 60 years.
Laparoscopic surgery of a rare giant paraesophageal hernia: a case report
Authors: Lukman Kiki , Rudiman Reno , Irawan Elit , Nugraha Prapanca
Published: August 2024

Introduction and Importance:

In the case of a hiatal hernia, the weakening of the esophageal hiatus allowed part of the stomach to slide to the mediastinum. Although the identification of hernias in esophageal hiatus is prone to subjectivity because of anatomical diversity, it is thought to occur often in radiological or endoscopic tests, with a range of 10–20% in the western population. Although asymptomatic, a rare form of hiatal hernia called a paraesophageal hernia (PEH) can be linked to serious, perhaps fatal consequences such as stomach volvulus. Only symptomatic patients should receive surgical treatment. In this case study, the authors present and discuss a giant PEH patient treated with laparoscopic hernial repair and fundoplication. A laparoscopic approach to PEH is important because of the shorter length of stay and fewer complications.

Case Presentation:

A 46-year-old Asian entered the hospital with symptoms of frequent dyspepsia syndrome, and from a computed tomography (CT) scan, she was diagnosed with a giant paraesophageal hernia. Hernia repair and fundoplication were performed laparoscopically. She was discharged three days after the surgery without significant complications.

Clinical Discussion:

This report represents a rare case of giant PEH. Although there are some limitations to laparoscopic surgery, it might be associated to fewer complication rate, a shorter stay in the hospital, and a faster recovery.

Conclusion:

Laparoscopic hernia repair and fundoplication is a safe and applicable surgery for people with symptomatic PEH.
Primary Cardiac Hemangiopericytoma on 18F-FDG and 68Ga-FAPI-04 PET/CT
Authors: Li Chuan , Deng Yichuan , Hu Xianwen
Published: August 2024

Hemangiopericytoma can occur anywhere in the body, mainly including the head and neck soft tissue, retroperitoneum, limbs, lung, pleura, pelvis, and meninges, whereas it arising in cardiac is rarely documented. Herein, we report 18F-FDG PET/CT and 68Ga-FAPI findings of hemangiopericytoma in the heart in a 23-year-old woman.
Elevated 68Ga-FAPI Activity in Tailgut Cyst Adenocarcinoma
Authors: Huang Yilin , Ou Lei , Zeng Chengrun , Chen Xiaoliang
Published: August 2024

Tailgut cyst adenocarcinoma is a rare malignant tumor. We present 68Ga-FAPI PET/CT findings of tailgut cyst adenocarcinoma in a 46-year-old woman. Tailgut cyst adenocarcinoma on 68Ga-FAPI PET/CT showed increased tracer uptake. This case demonstrates the potential value of 68Ga-FAPI PET/CT for evaluating tailgut cyst adenocarcinoma.
Bilateral Internal Auditory Canal Metastasis From Lung Cancer on FDG PET/CT
Authors: Xiao Liu , Li Lin , Wu Chunyan , Zhang Wenjie
Published: August 2024

The occurrence of metastatic tumor in the internal auditory canal is very rare. Thus, we report FDG PET/CT findings of bilateral Internal auditory canal metastasis from lung cancer in a 67-year-old man. FDG PET/CT and MRI showed nodules in the bilateral internal auditory canal with an SUVmax of 5.2. This case hints us that bilateral metastasis should be considered as differential diagnosis when we encounter bilateral nodule in the internal auditory.
Canalicular Cyst After Punctal Plug Insertion
Authors: Lee Dong Jun , Ahn Jung Hyo
Published: August 2024

This study describes the case of a patient with a canalicular cyst after punctal plug insertion. A 73-year-old male patient presented with a cystic mass on the right lower eyelid. He had undergone bilateral punctal occlusion with an absorbable punctal plug for dry eye syndrome 8 years ago. The lesion was palpable on the medial side of the right lower eyelid, accompanied by ectropion but without any inflammatory signs. Incision and drainage were performed, and a reduction in the size of the cystic mass was observed. Dacryocystography revealed cystic dilation of the right lower canaliculus, and a lacrimal probing test revealed right lower canalicular obstruction, leading to the diagnosis of a canalicular cyst. If a patient who has undergone punctal occlusion with punctal plugs presents with a mass in the medial canthus, a canalicular cyst should be considered in the differential diagnosis.
Ethical Issues in Normothermic Regional Perfusion in Controlled Organ Donation After Determination of Death by Circulatory Criteria: A Scoping Review
Authors: Murphy Nicholas B. , Slessarev Marat , Basmaji John , Blackstock Laurie , Blaszak Michael , Brahmania Mayur , Chandler Jennifer A. , Dhanani Sonny , Gaulton Matthew , Gross Jed A. , Healey Andrew , Lingard Lorelei , Ott Mary , Shemie Sam D. , Weijer Charles
Published: August 2024

Normothermic regional perfusion (NRP) is a surgical technique that can improve the quality and number of organs recovered for donation after the determination of death by circulatory criteria. Despite its promise, adoption of NRP has been hindered because of unresolved ethical issues. To inform stakeholders, this scoping review provides an impartial overview of the major ethical controversies surrounding NRP. We undertook this review according to a modified 5-step methodology proposed by Arksey and O’Malley. Publications were retrieved through MEDLINE and Embase. Gray literature was sourced from Canadian organ donation organizations, English-language organ donation organization websites, and through our research networks. Three reviewers independently screened all documents for inclusion, extracted data, and participated in content analysis. Disagreements were resolved through consensus meetings. Seventy-one documents substantively engaging with ethical issues in NRP were included for full-text analysis. We identified 6 major themes encompassing a range of overlapping ethical debates: (1) the compatibility of NRP with the dead donor rule, the injunction that organ recovery cannot cause death, (2) the risk of donor harm posed by NRP, (3) uncertainties regarding consent requirements for NRP, (4) risks to stakeholder trust posed by NRP, (5) the implications of NRP for justice, and (6) NRP’s potential to benefits of NRP for stakeholders. We found no agreement on the ethical permissibility of NRP. However, some debates may be resolved through additional empirical study. As decision-makers contemplate the adoption of NRP, it is critical to address the ethical issues facing the technique to ensure stakeholder trust in deceased donation and transplantation systems is preserved.
Neuronal network dynamics in the posterodorsal amygdala: shaping reproductive hormone pulsatility
Authors: Nechyporenko Kateryna , Voliotis Margaritis , Li Xiao Feng , Hollings Owen , Ivanova Deyana , Walker Jamie J. , O’Byrne Kevin T. , Tsaneva-Atanasova Krasimira
Published: August 2024

Normal reproductive function and fertility rely on the rhythmic secretion of gonadotropin-releasing hormone (GnRH), which is driven by the hypothalamic GnRH pulse generator. A key regulator of the GnRH pulse generator is the posterodorsal subnucleus of the medial amygdala (MePD), a brain region that is involved in processing external environmental cues, including the effect of stress. However, the neuronal pathways enabling the dynamic, stress-triggered modulation of GnRH secretion remain largely unknown. Here, we employ
in silico
modelling in order to explore the impact of dynamic inputs on GnRH pulse generator activity. We introduce and analyse a mathematical model representing MePD neuronal circuits composed of GABAergic and glutamatergic neuronal populations, integrating it with our GnRH pulse generator model. Our analysis dissects the influence of excitatory and inhibitory MePD projections’ outputs on the GnRH pulse generator’s activity and reveals a functionally relevant MePD glutamatergic projection to the GnRH pulse generator, which we probe with
in vivo
optogenetics. Our study sheds light on how MePD neuronal dynamics affect the GnRH pulse generator activity and offers insights into stress-related dysregulation.
Majorization requires infinitely many second laws
Authors: Hack Pedro , Braun Daniel A. , Gottwald Sebastian
Published: August 2024

Majorization is a fundamental model of uncertainty with several applications in areas ranging from thermodynamics to entanglement theory, and constitutes one of the pillars of the resource-theoretic approach to physics. Here, we improve on its relation to measurement apparatuses. In particular, after discussing what the proper notion of second law in this scenario is, we show that, for a sufficiently large state space, any family of entropy-like functions constituting a second law must be countably infinite. Moreover, we provide an analogous result for a variation of majorization known as thermo-majorization which, in fact, does not require any constraint on the state space provided the equilibrium distribution is not uniform. Finally, we discuss the applicability of our results to molecular diffusion and catalytic majorization. In this regard, we consider a variation of majorization used in plasma physics as a model of molecular diffusion and show that no finite family of entropy-like functions constituting a second law of molecular diffusion exists. Moreover, we show how our results are useful when dealing with a conjecture regarding catalytic majorization (i.e. trumping). In particular, we show that the sort of characterizations of trumping that have been considered before require an infinite family of real-valued functions.
Internal and external drivers interact to create highly dynamic mosquito blood-feeding behaviour
Authors: Tung Grayson A. , Fonseca Dina M.
Published: August 2024

Blood-feeding, which is necessary for most female mosquitoes to reproduce, provides an opportunity for pathogen transmission. Blood-feeding is influenced by external factors such as light, temperature, humidity and intra- and inter-specific interactions. Physiologically, blood-feeding cycles are linked to nutritional conditions and governed by conserved hormonal signalling pathways that prepare mosquito sensory systems to locate and evaluate hosts. Human activities also alter mosquito blood-feeding behaviour through selection pressures such as insecticide usage, habitat and ecosystem alterations, and climate change. Notably, blood-feeding behaviour changes within a mosquito’s lifespan, an underexplored phenomenon from an epidemiological standpoint. A review of the literature indicates that our understanding of mosquito biology and blood-feeding behaviour is predominantly based on studies of a handful of primarily tropical species. This focus likely skews our comprehension of the diversity of critical drivers of blood-feeding behaviour, especially under constraints imposed by harsh conditions. We found evidence of remarkable adaptability in blood-feeding and significant knowledge gaps regarding the determinants of host use. Specifically, epidemiological analyses assume host use is modified by external factors, while neglecting internal physiology. Integrating all significant factors is essential for developing effective models of mosquito-borne disease transmission in a rapidly changing world.
Fasting Plasma Glucose as a Primary Screening Test for the Diagnosis of Gestational Diabetes mellitus
Authors: Hasan Md. Rakibul , Sultana Nusrat , Panthi Sandesh , Hasan Mashfiqul , Jahan Sharmin , Aktar Yasmin , Hasanat Muhammad Abul
Published: August 2024

Aim

To see the diagnostic efficacy of fasting plasma glucose (FPG) in respect to OGTT during pregnancy.

Materials and Method

In this cross-sectional study, we enrolled 542 pregnant women 18 years or older by consecutive sampling irrespective of gestational age. 75gm three samples OGTT was done and categorized them to either normal glucose tolerance (NGT) or abnormal glucose tolerance (AGT) according to World Health Organization (WHO) 2013 criteria.

Results

The sensitivity of FPG with a threshold of 5.1mmol/L was 47.3% among the study subjects, which was very low but specificity was very high (99.7%). However, changing the cut off value to 4.7mmo/L and 4.5mmol/L significantly increased the sensitivity to 64.8% and 73.3% with modestly decreased specificity to 86.2% and 73.2% respectively. In pregnant women with gestational age 24 to 28 weeks, FPG with a threshold of 4.5mmol/L could identify 75% of GDM subjects with specificity 76.8%. Furthermore, it has the highest sensitivity in detecting AGT in all three trimesters (80%, 74.4% and 68%) compared to 4.7mmol/L (80%, 68.9% and 50%) and 5.1 (80%, 47.8% and 30%) in 1st, 2ndand 3rdtrimester respectively. FPG had positive correlation with maternal age (r=0.138, p=0.001), BMI (r=0.164, p<0.001) but negative correlation with weeks of gestation (r= -0.242, p<0.001).

Conclusion

FPG with cut off value of 4.5mmol/L may be used as an initial screening test for GDM to reduce the need for OGTT.
Evolution of the Spatial transcriptomic landscape during the progression of high-grade pancreatic intraductal papillary mucinous neoplasms to invasive cancer
Authors: Peng Sirui , Chen Qiangxing , Chen Zixin , Yao Mengling , Cai Yunqiang , He Du , Cai Yu , Cheng Ke , Li Jun , Cai He , Gao Pan , Gu Xiafei , Wang Xin , Li Yongbin , Zhang Man , Meng Lingwei , Xia Qi , Xu Panpan , Zhou Jin , Wu Zhong , Peng Bing
Published: August 2024

Intraductal papillary mucinous neoplasms (IPMN) is one of the known precancerous lesions. Patients’ prognosis is aggravated as IPMN transforms into invasive Pancreatic Ductal Adenocarcinoma (PDAC). The molecular mechanisms underlying this progression lack effective experimental models and urgently need to be elaborated. We performed spatial transcriptomics (ST) on fresh tissue samples from the same patient including normal pancreas, high-grade IPMN, and invasive PDAC, and described the step-by-step development of transcriptional landscape including clone evolution and adjacent TME feature variation. Our findings identified the master transcript factors and critical signaling pathways promoting IPMN progression to invasive PDAC. Additionally, both IPMN and PDAC harbored the ELF3, MYC, and KLF4 amplification. The Spatial CNV profile demonstrated significant heterogeneity among PDAC in their spatial distribution compared to IPMN, with seven distinct subclones showing diverse functions, such as hypoxia, oxidative phosphorylation, and epithelial-mesenchymal Transition. We observed a marked shift in the immune landscape, with the depletion of CD4+ T-cells and dendritic cells and an increase in immune-suppressive M2 macrophages in invasive PDAC, indicating a transition to an immune-evasive microenvironment. Additionally, cancer-associated fibroblasts (CAFs), particularly myofibroblastic CAFs, were enriched adjacent to invasive PDAC, suggesting their active role in tumor progression. By leveraging spatial transcriptomic analysis, our study provides comprehensive insights into the intricate molecular landscape that underlies the progression of IPMNs to invasive PDAC. These findings not only enhance our understanding of this complex process but also offer valuable knowledge for early diagnosis and intervention.

Highlights

Spatial CNV analysis reveals clonal evolution and distinct subclones in PDAC.

Key drivers like ELF3, MYC, and KLF4 are amplified in both IPMN and invasive PDAC.

Immune landscape shifts from pro-inflammatory in IPMN to immune-evasive in PDAC.

Enrichment of myofibroblastic CAFs suggests their role in tumor progression
Rough Grouping Enhances YOLO’s Pollinator Classification and Detection from Small Datasets
Authors: Kim Suyeon
Published: August 2024

This study addresses the challenges in pollinator monitoring by proposing an effective data structure for automated systems, with a focus on the use of machine learning to handle underrepresented groups in small datasets. By experimenting with grouping the top three pollinators (bee, butterfly, hoverfly) and non-pollinators in datasets of fewer than 300 samples, the research aims to enhance classification and detection accuracy. During 4-hour filming sessions, 181 images of insects larger than 1 cm were captured and classified into three grouping methods: “Pollinator/ Non-pollinator”, “Bee/Butterfly/Hoverfly/Ant”, and “Bumblebee/Honeybee/Butterfly/Hoverfly/ Ant”. YOLO V8 models were trained, validated, and tested with these datasets based on different class grouping methods. The study found that the “Pollinator/Non-pollinator” YOLOv8 model performed best across all metrics, suggesting it is more reliable for categorizing groups and detecting target objects, especially with smaller, imbalanced datasets. This finding aligns with the trend in machine learning that providing more training opportunities for individual classes improves accuracy. Therefore, using broader categorization methods can enhance the reliability and accuracy of automated monitoring systems when training data is insufficient.
Continued T12 transmission and shared antibiotic resistance during 2018-2023Vibrio choleraeoutbreaks in Cameroon
Authors: Ngomtcho Sen Claudine Henriette , Akenji Blaise Mboringong , Ndip Roland , Azman Andrew S , Tayimetha Yanick Carolle , Guenou Etienne , Engamba Sylvain , Okomo Marie Claire Assoumou , Lessler Justin , Wohl Shirlee
Published: August 2024

Seventh pandemicVibrio choleraewas first identified in Cameroon in 1971, causing several sporadic disease clusters with few cases. More recent years have seen larger cholera outbreaks, but the mechanism behind these periodic outbreaks is poorly understood, and it is unclear the degree to which antibiotic resistant strains contribute to disease burden and spread. We used whole genome sequencing to characterize 14V. choleraeisolates from the 2020 and 2021-2023 cholera epidemics in Cameroon. All these isolates belonged to the T12 lineage, and most showed the same antimicrobial resistance (AMR) pattern regardless of year. This suggests that cholera outbreaks in Cameroon are, at least in part, a continuation of the outbreaks previously reported in 2018 and as far back as 2012. This finding has important implications for cholera management since it suggests the ongoing presence of pathogenic cholera even in years with few reported cases. Similarly, the AMR results suggest the need for new treatment approaches, as resistance to many common antibiotics was found even within our limited sample set. As such, whole genome sequencing should be implemented in low-income countries such as Cameroon to improve disease surveillance and to detect and predict pathogen antibiotic resistance profiles.
Comparative Performance of an AI Tool and First-Year Residents for Retinal Disease and Glaucoma Assessments: A Study in a Mexican Tertiary Care Setting
Authors: Camacho-García-Formentí Dalia , Baylón-Vázquez Gabriela , Arriozola-Rodríguez Karen , Avalos-Ramirez Enrique , Hartleben-Matkin Curt , Valdez-Flores Hugo , Hodelin-Fuentes Damaris , Noriega Alejandro
Published: August 2024

Background

Artificial intelligence (AI) shows promise in ophthalmology, but its potential on tertiary care settings in Latin America remains understudied. We evaluated a Mexican AI-powered screening tool, against first-year ophthalmology residents in a tertiary care setting in Mexico City.

Methods

We analysed 435 adult patients undergoing their first ophthalmic evaluation. AI and residents’ assessments were compared against expert annotations for retinal disease, cup-to-disk ratio (CDR) measurements, and glaucoma suspect classification. We also evaluated a synergistic approach combining AI and resident assessments.

Results

For glaucoma suspect classification, AI outperformed residents in accuracy (88.6% vs 82.9%,p= 0.016), sensitivity (63.0% vs 50.0%,p= 0.116), and specificity (94.5% vs 90.5%,p= 0.062). The synergistic approach deemed a higher sensitivity (80.4%) than ophthalmic residents alone or AI alone (p <0.001). AI’s CDR estimates showed lower mean absolute error (0.056 vs 0.105,p <0.001) and higher correlation with expert measurements (r= 0.728 vsr= 0.538). In retinal disease assessment, AI demonstrated higher sensitivity (90.1% vs 63.0% for medium/high-risk,p <0.001) and specificity (95.8% vs 90.4%,p <0.001). Furthermore, differences between AI and residents were statistically significant across all metrics. The synergistic approach achieved the highest sensitivity for retinal disease (92.6% for medium/high-risk, 100% for high-risk).

Conclusion

AI outperforms first-year residents in key ophthalmic assessments. The synergistic use of AI and resident assessments shows potential for optimizing diagnostic accuracy, highlighting the value of AI as a supportive tool in ophthalmic practice, especially for early-career clinicians.
Repurposing Ivermectin and ATRA as Potential Therapeutics for Glioblastoma Multiforme
Authors: Sayad Saed , Hiatt Mark , Mustafa Hazem
Published: August 2024

Background

Glioblastoma multiforme (GBM) is the most aggressive and lethal form of primary brain tumor, characterized by rapid growth and resistance to conventional therapies. Despite advances in treatment, most patients succumb to the disease within 15 months. Drug repurposing, which involves finding new uses for existing drugs, is a promising strategy to develop new GBM treatments faster and more cost-effectively.

Method

We obtained single-cell RNA sequencing (scRNA-seq) data (GSE84465) from the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) repository to compare gene expression in GBM neoplastic cells and non-neoplastic cells. We identified genes that were abnormally expressed in tumor cells and linked these genes to potential drug targets. To identify potential repurposed drugs for GBM, we leveraged the Chemical Entities of Biological Interest (ChEBI) database to assess the interaction of various compounds with the differentially expressed genes identified in the scRNA-seq analysis. We focused on compounds that could reverse the aberrant gene expression observed in GBM neoplastic cells.

Results

Our analysis suggests that ivermectin and all-trans-retinoic acid (ATRA) could be repurposed as effective treatments for GBM. Ivermectin, typically used as an antiparasitic, demonstrated strong anti-tumor activity by downregulating 40 of the top 100 upregulated genes in GBM, indicating its potential to suppress tumor growth. ATRA, known for promoting cell differentiation, upregulated 60 genes typically downregulated in GBM neoplastic cells, showing its potential to correct transcriptional dysregulation and support tumor suppression. These findings underscore the promise of drug repurposing to target key pathways in GBM, offering new therapeutic options for this aggressive cancer.

Conclusions

Our results provide compelling evidence that ivermectin and ATRA may be effective in treating GBM. The observed alterations in gene expression indicate the ability of these two agents to disrupt key genes and pathways crucial for tumor progression. Given the increasing interest in drug repurposing for cancer treatment, comprehensive preclinical and clinical investigations are warranted to assess fully the therapeutic efficacy of these compounds against this disease.
The genotype-phenotype correlation of NR5A1 variants in 46,XY individuals: a study protocol
Authors: Dallago Renata Thomazini , Batista Rafael Loch , de Mendonça Berenice Bilharinho , Nogueira Vania dos Santos Nunes
Published: August 2024

Introduction

Disorders of sex development (DSDs) were defined as congenital conditions in which the development of chromosomal, gonadal and anatomic sex is atypical. Nuclear receptor subfamily 5 group A member 1 (NR5A1), previously known as steroidogenic factor 1 (SF1) plays a crucial role in transcriptional regulation of genes involved in steroidogenesis, adrenal and gonadal development, and reproduction.NR5A1emerged to be causative of 10 to 20% of 46,XY DSD.

Objective

The present study aims to perform a systematic review evaluating the association between phenotype and genotype in patients withNR5A1defects and 46,XY DSD looking for outcomes of spontaneous puberty, change of gender and social sex.

Method

The proposed systematic review will be conducted in accordance with the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. This review will consider observational studies, including prospective and retrospective cohort studies, cross sectional, case series and case reports studies. We will focus on studies that included patients with allelic variants in theNR5A1gene and 46,XY DSD. This review will consider studies that include the outcomes of spontaneous puberty, gender change and genotype/phenotype correlation associating the types of variants with the degree of external genitalia virilization.

Conclusion

Results of this review can help in the management and clinical understanding of patients withNR5A1defects and 46,XY DSD.
Efficacy of intravenous paracetamol and mannitol in managing chronic post-thoracotomy pain in patients with lung cancer: Study protocol for a single center prospective randomized double-blind controlled trial
Authors: Lu Xing , Zhou Junhui , Li Xi , Gao Jie , Liu Siqing , Zhong Wei , Xi Gaoyuan , Guo Yingchun , Xu Hongdang
Published: August 2024

Chronic post-thoracotomy pain is a common complication that affects 20% to 60% of patients who undergo surgery for lung cancer. The persistent pain affects quality of life and satisfaction with surgery. Intravenous paracetamol and mannitol, known to have analgesic and antipyretic properties, may help relieve moderate-to-severe post-operative pain. This trial aims to assess their effectiveness and safety in managing chronic post-thoracotomy pain in patients with lung cancer. This prospective double-blind randomized controlled clinical trial will be conducted at a single center. A total of 856 patients who will undergo thoracoscopic radical surgery for lung cancer will be enrolled and randomly assigned to test (intravenous paracetamol and mannitol) and control (intravenous normal saline) groups in a 1:1 ratio (428 patients in each group). Efficacy will be evaluated in terms of the incidence of chronic post-thoracotomy pain at 3 months (primary outcome). Secondary outcomes will include the dosage of propofol and remifentanil, numerical rating scale pain scores, number of times the patient-controlled intravenous analgesia button is pressed, occurrence of post-operative nausea and vomiting and respiratory depression, time to first flatus and ambulation after surgery, length of hospital stay, surgeon and patient satisfaction, and incidence of chronic post-thoracotomy pain at 6 and 12 months after surgery. Quality of daily life will be evaluated at 3, 6, and 12 months after surgery. Intention-to-treat analysis will also be conducted. The research protocol has been reviewed and approved by the Medical Thesis Committee of Henan Provincial Chest Hospital and Chest Hospital of Zhengzhou University on April 29, 2023 (reference: [2023] approval number: [04-06]). The results of this trial will be communicated to the participants and subsequently submitted for publication in peer-reviewed journals for wider dissemination. The study has been registered in the Chinese Clinical Trial Registry on June 27, 2023 (registration number: ChiCTR2300072869, available athttps://www.chictr.org.cn/).The protocol version number is Version 1.1, dated August 20, 2023.
Can Psychedelic Use Benefit Meditation Practice? Examining Individual, Psychedelic, and Meditation-Related Factors
Authors: Jiwani Zishan , Goldberg Simon B. , Stroud Jack , Young Jacob , Curtin John , Dunne John D. , Simonsson Otto , Webb Christian A. , Carhart-Harris Robin , Schlosser Marco
Published: August 2024

Introduction

Meditation practice and psychedelic use have attracted increasing attention in the public sphere and scientific research. Both methods induce non-ordinary states of consciousness that may have significant therapeutic benefits. Thus, there is growing scientific interest in potential synergies between psychedelic use and meditation practice with some research suggesting that psychedelics may benefit meditation practice. The present study examined individual, psychedelic-related, and meditation-related factors to determine under what conditions meditators perceive psychedelic use as beneficial for their meditation practice.

Method

Participants (N= 863) who had reported psychedelic use and a regular meditation practice (at least 3 times per week during the last 12 months) were included in the study. To accommodate a large number of variables, machine learning (i.e., elastic net, random forest) was used to analyze the data.

Results

Most participants (n= 634, 73.5%) found psychedelic use to have a positive influence on their quality of meditation. Twenty-eight variables showed significant zero-order associations with perceived benefits even following a correction. Elastic net had the best performance (R2= .266) and was used to identify the most important features. Across 53 variables, the model found that greater use of psychedelics, intention setting during psychedelic use, agreeableness, and exposure to N,N-Dimethyltryptamine (N,N-DMT) were most likely to be associated with the perception that psychedelics benefit meditation practice. The results were consistent across several different approaches used to identify the most important variables (i.e., Shapley values, feature ablation).

Discussion

Results suggest that most meditators found psychedelic use to have a positive influence on their meditation practice, with: 1) regularity of psychedelic use, 2) the setting of intentions for psychedelic use, 3) having an agreeable personality, and 4) reported use of N,N-DMT being the most likely predictors of perceiving psychedelic use as beneficial. Longitudinal designs and randomized trials manipulating psychedelic use are needed to establish causality.