bluuebunny/crossref_metadata_2025 huggingface dataset:
The characteristics of mRNA m6A methylomes in allopolyploid Brassica napus and its diploid progenitors
Authors: Li Zeyu , Li Mengdi , Wu Xiaoming , Wang Jianbo
Published: October 2022

Genome duplication events, comprising whole-genome duplication and single-gene duplication, produce a complex genomic context leading to multiple levels of genetic changes. However, the characteristics of m6A modification, the most widespread internal eukaryotic mRNA modification, in polyploid species are still poorly understood. This study revealed the characteristics of m6A methylomes within the early formation and following the evolution of allopolyploid Brassica napus. We found a complex relationship between m6A modification abundance and gene expression level depending on the degree of enrichment or presence/absence of m6A modification. Overall, the m6A genes had lower gene expression levels than the non-m6A genes. Allopolyploidization may change the expression divergence of duplicated gene pairs with identical m6A patterns and diverged m6A patterns. Compared with duplicated genes, singletons with a higher evolutionary rate exhibited higher m6A modification. Five kinds of duplicated genes exhibited distinct distributions of m6A modifications in transcripts and gene expression level. In particular, tandem duplication-derived genes showed unique m6A modification enrichment around the transcript start site. Active histone modifications (H3K27ac and H3K4me3) but not DNA methylation were enriched around genes of m6A peaks. These findings provide a new understanding of the features of m 6A modification and gene expression regulation in allopolyploid plants with sophisticated genomic architecture.
A tale of two cities: the education and experiences of two ICJ judges in China and America
Authors: Chen Li
Published: October 2022

This article draws upon multi-archival research to rediscover the experiences and research of Judges VK Wellington Koo and Shi Jiuyong at St John’s University in Shanghai and Columbia University in New York City. The former was the first Chinese person to be elected Vice President of the International Court of Justice while the latter became the first Chinese person to helm the Court. It aims to offer crucial insights into the making of these two eminent international judges from China and their perceptions of international law. More importantly, it sheds light on the movement of people—missionaries, law professors and diplomats—and the circulation of their ideas as drivers of the expansion of international law. This article strives to examine these understudied major figures to make the legal history of international dispute settlement more geographically and racially inclusive.
A Matter of the Heart: Why It Is Time to Change How We Talk About Maternal Mortality
Authors: Lord Megan
Published: October 2022

As the global burden of disease shifts from “diseases of poverty” such as diarrhea to “diseases of affluence” like diabetes and heart disease, a parallel shift is underway in maternal health. Maternal death from hemorrhage is decreasing, while deaths resulting from exacerbation of underlying chronic disease are on the rise.
Core orientations and magnetic fields in isolated molecular clouds
Authors: Sharma Ekta , Gopinathan Maheswar , Soam Archana , Lee Chang Won , Seshadri T R
Published: October 2022

Molecular clouds are sites of star formation. Magnetic fields are believed to play an important role in their dynamics and shaping morphology. We aim to study any possible correlation that might exist between the magnetic fields orientation inside the clouds and the magnetic fields at envelope scales and their connection with respect to the observed morphology of the selected clouds. We examine the magnetic field orientation towards the clouds L1512, L1523, L1333, L1521E, L1544, L1517, L1780, and L183, using optical and Planck polarization observations. We also found the correlation between the ambient magnetic field and core orientations derived using Astrodendrogram on the Herschel 250 $\mu$m data. We find that the magnetic fields derived from optical and Planck agree with each other. The derived magnetic fields are aligned along the observed emission of each cloud as seen in Herschel 250 $\mu$m data. We also find that the relative orientation between the cores and the magnetic fields is random. This lack of correlation may arise due to the fact that the core orientation could also be influenced by the different magnetization within individual clouds at higher densities or the feedback effects which may vary from cloud to cloud. The estimated magnetic field strength and the mass-to-flux ratio suggest that all the clouds are in a magnetically critical state except L1333, L1521E, and L183, where the cloud envelope could be strongly supported by the magnetic field lines.
Efficiency of the top-down polycyclic aromatic hydrocarbon-to-fullerene conversion in ultraviolet irradiated environments
Authors: Murga M S , Akimkin V V , Wiebe D S
Published: October 2022

Polycyclic aromatic hydrocarbons (PAHs) and fullerenes play a major role in the physics and chemistry of the interstellar medium (ISM). Based on a number of recent experimental and theoretical investigations we developed a model in which PAHs are subject to photo-dissociation (carbon and hydrogen loss) and hydrogenation. We take into account that dehydrogenated PAHs may fold into closed structures – fullerenes. Fullerenes, in their turn, can be also hydrogenated, becoming fulleranes, and photo-dissociated, losing carbon and hydrogen atoms. The carbon loss leads to shrinking of fullerene cages to smaller ones. We calculate the abundance of PAHs and fullerenes of different sizes and hydrogenation level depending on external conditions: the gas temperature, intensity of radiation field, number density of hydrogen atoms, carbon atoms, and electrons. We highlight the conditions, which are favourable for fullerene formation from PAHs, and we conclude that this mechanism works not only in H-poor environment but also at modest values of hydrogen density up to 104 cm−3. We found that fulleranes can be formed in the ISM, although the fraction of carbon atoms locked in them can be maximum around 10−9. We applied our model to two photo-dissociation regions, Orion Bar and NGC 7023. We compare our estimates of the fullerene abundance and synthetic band intensities in these objects with the observations and conclude that our model gives good results for the closest surroundings of ionizing stars. We also demonstrate that additional fullerene formation channels should operate along with ultraviolet (UV)-induced formation to explain abundance of fullerenes far from UV sources.
Cellular immunotherapy for medulloblastoma
Authors: Schakelaar Michael Y , Monnikhof Matthijs , Crnko Sandra , Pijnappel Emma W , Meeldijk Jan , ten Broeke Toine , Bovenschen Niels
Published: October 2022

Medulloblastoma (MB) is the most common malignant brain tumor in children, making up ~20% of all primary pediatric brain tumors. Current therapies consist of maximal surgical resection and aggressive radio- and chemotherapy. A third of the treated patients cannot be cured and survivors are often left with devastating long-term side effects. Novel efficient and targeted treatment is desperately needed for this patient population. Cellular immunotherapy aims to enhance and utilize immune cells to target tumors, and has been proven successful in various cancers. However, for MB, the knowledge and possibilities of cellular immunotherapy are limited. In this review, we provide a comprehensive overview of the current status of cellular immunotherapy for MB, from fundamental in vitro research to in vivo models and (ongoing) clinical trials. In addition, we compare our findings to cellular immunotherapy in glioma, an MB-like intracranial tumor. Finally, future possibilities for MB are discussed to improve efficacy and safety.
Survived and disappeared intra-oceanic arcs of the Paleo-Asian Ocean: evidence from Kazakhstan
Authors: Safonova Inna , Perfilova Alina
Published: October 2022

This paper reviews published and presents new data on U-Pb detrital zircon ages, and petrographic, geochemical and isotope (Sm-Nd, Lu-Hf) compositions obtained from greywacke sandstones of Kazakhstan in order to reconstruct fossil intra-oceanic arcs that once existed at Pacific-type convergent margins of the Paleo-Asian Ocean (PAO) in Paleozoic time. We focus on orogenic belts of central Kazakhstan (Itmurundy and Tekturmas) and eastern Kazakhstan (Zharma and Char) in the western Central Asian Orogenic belt. These orogenic belts host accretionary complexes with greywacke sandstones of early Paleozoic (central Kazakhstan) and middle-late Paleozoic (eastern Kazakhstan) ages. First, we evaluate general perspectives for studying sandstones to reconstruct survived and disappeared magmatic arcs, taking into account episodes of subduction erosion. Then we discuss the analytical data from sandstones to make conclusions about the ages and formation settings of their igneous protoliths and define maximum deposition ages. Finally, we discuss the role of serpentinite mélanges in tectonic reconstructions. We argue that sandstones hosted by accretionary complexes are typically greywackes deposited close to their igneous sources and buried rapidly. The provenances of the studied greywacke sandstones of central and eastern Kazakhstan were dominated by mafic to andesitic igneous protoliths derived from juvenile mantle sources. The igneous rocks in the provenances were emplaced in an intra-oceanic arc setting. The sandstones were deposited in fore-arc/trench basins or, to a lesser degree, in back-arc basins. The data from both sandstones and serpentinite mélanges reconstruct middle-late-Cambrian, Ordovician, late-Devonian and Carboniferous arcs of the western PAO. The middle-late Cambrian arcs were fully destroyed by subduction erosion, whereas the Ordovician and Carboniferous arcs survived. The late-Devonian arcs were also eroded, but partly. Both the early and late Paleozoic active margins of the PAO were characterized by alternating periods of accretionary growth and subduction erosion.
Type 3c
Authors: Vonderau Jennifer Shurney , Desai Chirag S.
Published: October 2022

Type 3c diabetes, also known as pancreatogenic diabetes, occurs when primary pancreatic disorders damage the pancreatic islets of Langerhans. Although often misdiagnosed as type 2 diabetes, type 3c diabetes is different in cause, clinical presentation, treatment, and prognosis. Patients with type 3c diabetes are more likely to experience complications and death related to hypoglycemic events. This article reviews the causes and management of type 3c diabetes, which is estimated to affect 5% to 10% of all patients with diabetes.
Improving Cephalad Lag Screw Placement in the Femoral Head During Cephalomedullary Nailing Using a Novel Augmented Reality System
Authors: Konda Sanjit R. , Solasz Sara , Derken Meghan , Ganta Abhishek , Egol Kenneth A.
Published: October 2022

Objectives:

To measure the effect of a novel augmented reality software designed to aid in lag screw placement into the femoral head for cephalomedullary nails.

Design:

Retrospective cohort study.

Setting:

Single Level I trauma center.

Patients:

Between November 2017 and December 2020, 114 consecutive patients with a hip fracture that underwent repair with a cephalomedullary nail by one of 2 orthopaedic trauma surgeons were reviewed. Fracture classifications included OTA/AO 31-A1, 31-A2, 31-A3, and 31-B3.

Intervention:

The first 57 patients underwent fracture repair without the software (control) and the subsequent 57 patients underwent repair with use of the augmented reality software (AR).

Main Outcome Measurements:

Tip apex distance (TAD) and femoral head zone (AP: superior, center, inferior; Lateral: anterior, center, posterior) were measured using standardized techniques.

Results:

The mean TAD was lower for the AR versus control cohort (10.7 ± 2.9 mm vs. 15.4 ± 3.8 mm; P < 0.001). TAD <10 mm for AR versus control: 25 (43.9%) versus 3 (5.3%), P < 0.001. TAD <15 mm for AR versus control: 50 (87.7%) versus 44 (77.2%), P < 0.001. On the AP view, center position was achieved in 50.9% versus 7.0% of cases for the AR versus control cohort, respectively. On the lateral view, center position was achieved in 68.4% versus 12.3% of cases for the AR versus control cohort, respectively.

Conclusion:

This study suggests that use of the novel augmented reality software for assistance in lag screw positioning within the femoral head improves overall TAD and ability to achieve the center–center position.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Anxiety, Depression, and Social Skills in Girls with Fragile X Syndrome: Understanding the Cycle to Improve Outcomes
Authors: Lightbody Amy A. , Bartholomay Kristi L. , Jordan Tracy L. , Lee Cindy H. , Miller Jonas G. , Reiss Allan L.
Published: October 2022

Objective:

Female patients with fragile X syndrome (FXS), a genetic condition associated with a mutation in the FMR1 gene, are at significantly elevated risk for developing anxiety and depression. This study is designed to better understand these symptoms in school-age girls, particularly as they relate to age, social skills, and functional outcomes.

Methods:

We compared 58 girls aged 6 to 16 years with FXS with 46 age-matched, sex-matched, and developmentally matched peers without FXS on measures of anxiety, depression, social skills, adaptive behavior, and quality of life.

Results:

Girls with FXS 10.5 years and older demonstrated significantly higher levels of depression, withdrawal, and social avoidance than girls younger than 10.5 years with FXS (p-values < 0.01). Girls in the comparison group did not show any age-related differences on these measures. The older FXS cohort also showed associations between social communication and interaction skills, adaptive behavior, and measures of anxiety and depression (p-values < 0.05) not seen in the comparison group, regardless of age.

Conclusion:

We found that age seems to play an important role in the development of mood symptoms and that such symptoms are uniquely correlated with social communication and reciprocal social interaction behaviors and adaptive functioning in girls with FXS after puberty. These data suggest a critical window of intervention for girls with FXS in the improvement of social interaction skills and the prevention of social avoidance and symptoms of anxiety and depression, with the ultimate goal of improving quality of life and promoting greater independence.
Association of hormone therapy and changes of objective sleep quality in women of late menopausal transition with sleep disorder: a preliminary study
Authors: Kang Soyeon , Kwon Dong Jin , Hong Jiyeon , Go Minji , Chung Youn-Jee , Kim Mee-Ran , Kim Miji , Cho Hyun Hee , Jeung In Cheul
Published: October 2022

Objective

The aim of this study was to investigate changes in objective sleep quality with hormone therapy (HT) in women with late menopausal transition.

Methods

Healthy midlife women with sleep difficulty who received HT were included. Those undergoing late menopausal transition were screened. Sleep patterns and self-reported questionnaires were collected before and 10 weeks after starting HT.

Results

Ten women who met the criteria (age, 50.1 ± 2.8 years) showed higher sleep efficiency and shorter wakefulness after sleep onset (WASO) 10 weeks after starting HT. However, no significant change was found in objective sleep quality after adjustment for multiple comparisons: sleep efficiency, 84.2 ± 7.7 versus 88.2% ± 4.7%, P = 0.037, adjusted P = 0.259; WASO, 59.0 ± 27.2 minutes versus 41.4 ± 17.4 minutes, P = 0.020, adjusted P = 0.140; average duration per awakening, 2.9 ± 1.0 minutes versus 2.2 ± 0.5 minutes, P = 0.033, adjusted P = 0.231. A better score of subjective sleep quality in the Pittsburgh Sleep Quality Index was observed 10 weeks after starting HT (2.0 ± 0.0 vs 1.2 ± 0.4, P = 0.006, adjusted P = 0.042), but sensitivity analysis did not show consistent results after adjustment for multiple comparisons (2.0 ± 0.0 vs 1.1 ± 0.4, P = 0.020, adjusted P = 0.140). Total scores of the Insomnia Severity Index and Menopause Rating Scale were better 10 weeks after starting HT (Insomnia Severity Index, 14.7 ± 3.0 vs 9.1 ± 3.8, P = 0.010; Menopause Rating Scale, 29.0 ± 5.2 vs 21.6 ± 3.0, P = 0.009) with consistent results in sensitivity analyses. There was no difference in the Epworth Sleepiness Scale before and after HT (7.2 ± 1.7 vs 8.6 ± 4.5, P = 0.309). The change in each objective sleep quality variable before and after HT showed strong positive or negative correlations with the change in only a few items in subjective sleep quality.

Conclusion

Women in the late menopausal transition period showed higher sleep efficiency and shorter WASO after HT; however, multiple comparisons showed no statistically significant difference in objective sleep quality between before and after HT.
Effects of resistance training on C-reactive protein in menopausal and postmenopausal women: a systematic review and meta-analysis of randomized controlled trials
Authors: Loaiza-Betancur Andrés F. , Gómez-Tomás Cinta , Blasco José María , Chulvi-Medrano Iván , Iglesias-González Lisette Ethel
Published: October 2022

Importance

Menopause is a biological stage associated with increased cardiovascular morbidity and mortality due to changes in sex hormone levels.

Objective

This systematic review aimed to investigate the benefits and harms of RT in menopausal and postmenopausal women.

Evidence Review

We searched PubMed, Embase, CENTRAL, Scopus, and Web of Science from inception to 2021, and clinical trial registries. Randomized controlled trials (RCT) in menopausal and postmenopausal women that compared women undergoing RT programs with a control group were included. The primary outcomes were C-reactive protein level and adverse events; and, the secondary outcomes were lipid profile and waist circumference. Two reviewers independently selected the studies, extracted data, and assessed the completeness of RT programs, risk of bias, and quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach (GRADE). A random-effects model was used. Statistical significance was set at P < 0.05.

Findings

Twelve RCTs published from 2012 to 2020 met the inclusion criteria (n = 482). Four follow-up periods were assessed. RT caused reductions in C-reactive protein levels compared to those in the control group in postmenopausal women in the short- to long-term follow-up (mean difference, −0.47 mg/dL; 95% confidence interval, −0.66 to −0.29; P < 0.00001). Furthermore, RT may reduce C-reactive protein levels even at moderate and moderate-to-high intensity (P < 0.0001 and P = 0.0005, respectively). Similar findings were found for lipid profiles in the short- to long-term follow-up (P < 0.05). RT may have had little to no effect on waist circumference. The certainty of the body of evidence was assessed as very low and downgraded owing to serious study limitations, inconsistency, imprecision, and publication bias.

Conclusions and Relevance

There was very low-quality evidence supporting the benefits of RT compared with control for C-reactive protein levels and lipid profile. No benefits were found for the outcome of waist circumference in postmenopausal women with different comorbidities or risk factors. Safety data were scarce. We have little confidence in the results, and the true effect is likely to be substantially different. Further well-conducted and well-reported RCTs are warranted to strengthen the evidence.

Protocol registration

PROSPERO CRD42020213125.
Tenon Patch Graft With Vascularized Conjunctival Flap for Management of Corneal Perforation
Authors: Shekhawat Nakul Singh , Kaur Bhavleen , Edalati Armand , Abousy Mya , Eghrari Allen Omid
Published: October 2022

Purpose:

Traumatic paracentral corneal perforations may lead to irregular astigmatism and opacification from lamellar grafts. We present an alternative surgical technique using a Tenon patch graft and a conjunctival flap.

Methods:

A 42-year-old man presented with a 1-mm paracentral corneal perforation 6 weeks after penetrating trauma by a metallic foreign body. A region of Tenon fascia was excised and sutured to cover the perforation, and a conjunctival flap was then created and sutured over this Tenon graft. A bandage contact lens was placed postoperatively. Serial imaging was conducted to document healing including optical coherence tomography (OCT) and slit lamp photography.

Results:

At postoperative day 1, uncorrected distance visual acuity (UDVA) was hand motion, the anterior chamber was formed, and OCT revealed Tenon fascia and conjunctiva covering the defect. By postoperative week 2, the leak resolved and UDVA was 20/30. At postoperative week 4, UDVA improved to 20/20, the Tenon graft was noted to be undergoing contraction, and a single feeder vessel remained prominent in the conjunctival flap. By postoperative month 4, UDVA was 20/25 and only mild paracentral cornea clouding was noted. Initial, focal steepening and thickening normalized by month 4 leaving mild, normal astigmatism. OCT revealed integration of the Tenon graft into the corneal stroma.

Conclusions:

For paracentral corneal perforations, a Tenon patch graft in conjunction with a conjunctival flap may aid healing with favorable postoperative refractive outcomes.
The Role of Physical Therapy in Reducing the Recurrence of Clogged Milk Ducts and Subsequent Mastitis
Authors: McMeans Shana , Gantt Emily , Rhodes Stephanie , Wood Stacie , Divine Kate , McVey Lisa
Published: October 2022

Background:

The World Health Organization supports and recognizes the benefits of breastfeeding, at least 6 months or more, for both a mother and her baby. A common cause for cessation of breastfeeding is the development of mastitis typically caused by a clogged milk duct. Literature is limited on physical therapy's role in reducing clogged milk ducts and subsequent mastitis.

Study Design:

A case report

Case Description:

This case describes a 33-year-old woman who was referred to physical therapy following unsuccessful treatment for breastfeeding complications that included daily bilateral clogged milk ducts and mastitis. The patient participated in a comprehensive physical therapy approach consisting of patient education, moist heat, therapeutic ultrasound, manual techniques, and cryotherapy.

Outcomes:

A retrospective review of 5 physical therapy visits over 3 weeks was completed. The patient reported no recurrence of mastitis and the ability to manage and decrease the recurrence of clogged milk ducts. The patient's number of daily clogged milk ducts and reported success with breastfeeding improved. At 6 months post-discharge, the patient reported she was able to continue breastfeeding and had no recurrence of mastitis.

Discussion:

Physical therapists may have a potential role in treating clogged milk ducts and subsequent mastitis in postpartum women where there is a lack of availability of lactation resources.

A video abstract is available (see Supplemental Digital Content 1, available at: http://links.lww.com/JWHPT/A84).
Use of anti-Müllerian hormone for understanding ovulatory dysfunction in polycystic ovarian syndrome
Authors: Aydogan Mathyk Begum , Cetin Esra , Yildiz Bulent O.
Published: October 2022

Purpose of review

The aim of this review is to understand how anti-Müllerian hormone (AMH) contributes to ovulatory dysfunction in polycystic ovarian syndrome (PCOS).

Recent findings

In the last few years, new findings have emerged on AMH and its role on the central nervous system causing ovulatory dysfunction.

Anovulation is a prominent feature of PCOS. Women with anovulatory PCOS have higher AMH levels than in ovulatory PCOS. Higher levels of AMH may contribute to the pathophysiology of PCOS through central and peripheral actions. Once universal standardization is achieved to measure serum AMH, the benefits would be significant in diagnosing women with PCOS.
Endobariatrics: well past infancy and maturing rapidly
Authors: Shrestha Shreesh , Shrestha Esha , Shah Tilak
Published: October 2022

Purpose of review

This review summarizes the key developments with regard to FDA-approved endoscopic bariatric metabolic therapies (EBMTs) in the last 2 years.

Recent findings

The prevalence of obesity has increased during the coronavirus disease 2019 (COVID-19) pandemic, and obesity worsens COVID-19 related outcomes. Several studies have confirmed the safety and short-term efficacy of intragastric balloons (IGBs). In the short-term IGBs may improve steatosis and fibrosis in nonalcoholic fatty liver disease and improve quality of life and mental health. Unfortunately weight loss from these temporarily placed devices is not sustained long-term. Endoscopic sleeve gastroplasty (ESG) may be more effective and durable than IGBs, and result in fewer adverse events compared to bariatric surgery. The recently completed MERIT trial may catapult ESG as a first-line EBMT. Aspiration therapy meets safety and effectiveness thresholds for incorporation into routine practice, but overall acceptance has been lower than other FDA-approved EBMTs.

The field of endobariatrics is rapidly maturing. Significant knowledge gaps remain with regards to combining EBMTs with pharmacologic therapy to improve durability of weight loss. The rapid expansion in the literature supporting safety and long-term efficacy ESG may prompt revision of existing guidelines.
Probiotics for the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications
Authors: Szajewska Hania , Berni Canani Roberto , Domellöf Magnus , Guarino Alfredo , Hojsak Iva , Indrio Flavia , Lo Vecchio Andrea , Mihatsch Walter A. , Mosca Alexis , Orel Rok , Salvatore Silvia , Shamir Raanan , van den Akker Chris H. P. , van Goudoever Johannes B. , Vandenplas Yvan , Weizman Zvi ,   on behalf of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications
Published: October 2022

Background:

Probiotics, defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are widely used despite uncertainty regarding their efficacy and discordant recommendations about their use. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications provides updated recommendations for the use of probiotics for the management of selected pediatric gastrointestinal disorders.

Methods:

All systematic reviews and/or meta-analyses, as well as subsequently published randomized controlled trials (RCTs) (until December 2021), that compared the use of probiotics in all delivery vehicles and formulations, at any dose, with no probiotic (ie, placebo or no treatment), were eligible for inclusion. The recommendations were formulated only if at least 2 RCTs on a similar well-defined probiotic strain were available. The modified Delphi process was used to establish consensus on the recommendations.

Results:

Recommendations for the use of specific probiotic strains were made for the management of acute gastroenteritis, prevention of antibiotic-associated diarrhea, nosocomial diarrhea and necrotizing enterocolitis, management of Helicobacter pylori infection, and management of functional abdominal pain disorders and infant colic.

Conclusions:

Despite evidence to support the use of specific probiotics in some clinical situations, further studies confirming the effect(s) and defining the type, dose, and timing of probiotics are still often required. The use of probiotics with no documented health benefits should be discouraged.
Atypical Presentation of Monkeypox Virus Infection in a Postvaccinated Altered Immunocompetent Patient—A Case-Report
Authors: Taleb Eyal , Zucker Roy , Wagner-Kolasko Gal , Raviv Yuval
Published: October 2022

We herein report a case of an altered immunocompetent patient with atypical monkeypox presentations after being vaccinated with JYNNOES vaccine. The initial presentation was of acute bacterial paronychia. This incident suggests the need for individuals at high-risk for monkeypox infection with altered immunity to receive 2 vaccination doses.
Restoration of Grasp after Single-Stage Free Functioning Gracilis Muscle Transfer In Traumatic Adult Pan Brachial Plexus Injury
Authors: Maldonado Andres A. , Poppler Louis , Kircher Michelle F. , Spinner Robert J. , Bishop Allen T. , Shin Alexander Y.
Published: October 2022

Introduction:

A variety of approaches have been described to obtain rudimentary grasp following traumatic pan brachial plexus injury in the adult. The aim of this study is to evaluate hand prehension after a Gracilis Single-Stage Free Functioning Muscle Transfer (SSFFMT).

Materials and Methods:

Twenty-seven patients who underwent gracilis SSFFMT for elbow flexion and hand prehension following a pan-plexus injury were included. All patients presented with a minimum of 2 years of follow-up. Postoperative finger flexion, elbow flexion strength, preoperative and postoperative DASH scores, secondary hand procedures, complications as well as demographic characteristics were analyzed.

Results:

Twenty patients (74%) demonstrated active finger pull-through. Only 6 (25%) patients considered their hand function as useful for daily activities. DASH score improved by 13.1 ± 13.7 (p-value < 0.005). All patients were expected to require one secondary procedure: combined wrist, thumb CMC and thumb IP fusions, as no extensor reconstruction was performed. These were actually performed in 89%, 78% and 74% of patients, respectively. Four postoperative complications included hematoma, seroma, wound dehiscence and skin paddle loss. No flap loss occurred.

Conclusion:

In pan-plexus injuries, the use of a gracilis SSFFMT is an alternative to the Doi double FFMT procedure and cC7 transfer, especially for patients that cannot afford (economically or mentally) two to three important surgeries in a short period of time. Further research and studies are required to improve hand function in these patients.
Acute Flaccid Myelitis: Review of Clinical Features, Diagnosis, and Management with Nerve Transfers
Authors: Kozlowski Julia , Linzey Joseph R. , Muhlestein Whitney E. , Smith Brandon W. , Chang Kate Wan-Chu , Yang Lynda J.-S.
Published: October 2022

OBJECTIVE

Acute flaccid myelitis (AFM) is a devastating neurological condition in children manifesting as acute limb weakness, paralysis, or both. Despite increased awareness of AFM following the initiation of U.S. surveillance in 2014, no consensus exists for its treatment. The purpose of this systematic review is to summarize the most current knowledge regarding AFM epidemiology, etiology, clinical features, diagnosis, and supportive and operative management, focusing on the promise of nerve transfers for this disease.

METHODS

The authors systematically reviewed the literature based on PRISMA guidelines using multiple databases to search the keywords (“acute flaccid myelitis”), (‘acute flaccid myelitis’/exp OR ‘acute flaccid myelitis’), and (Acute AND flaccid AND myelitis). Original articles were included if the studies reported on (1) the diagnosis of AFM and (2) patient-specific data regarding epidemiology, etiology, clinical features, diagnostic features, or management of AFM.

RESULTS

Of 843 articles initially identified, 99 were included in this review. The precise etiology and pathophysiologic mechanism of AFM is yet to be definitively determined, but AFM is strongly associated with non-polio enterovirus infections. Clinical presentation typically comprises preceding viral prodrome, pleocytosis, spinal cord lesions on T2 MRI, and acute onset of flaccid weakness/paralysis with hyporeflexia in at least one extremity. Supportive care includes medical therapy and rehabilitation, though patients treated conservatively often have persistent neurological deficits. Early studies of nerve transfer for AFM have shown favorable outcomes for patients with persistent weakness.

CONCLUSIONS

Supportive care and physical therapy are the foundation of a multi-disciplinary approach to managing AFM. However, for patients with persistent limb weakness, nerve transfer has shown promise for improving function, particularly in distal muscle groups. When evaluating a patient for nerve transfer, surgeons must consider potential spontaneous recovery, patient selection, donor nerve availability, recipient nerve appropriateness, and procedure timing.
Modeling the Risk of HIV Transfusion Transmission
Authors: Belov Artur , Yang Hong , Forshee Richard A. , Whitaker Barbee I. , Eder Anne F. , Chancey Caren , Anderson Steven A.
Published: October 2022

Background:

Blood donations are routinely screened for HIV to prevent an infectious unit from being released to the blood supply. Despite improvements to blood screening assays, donations from infected donors remain undetectable during the window period (WP), when the virus has not yet replicated above the lower limit of detection (LOD) of a screening assay. To aid in the quantitative risk assessments of WP donations, a dose–response model describing the probability of transfusion-transmission of HIV over a range of viral RNA copies was developed.

Methods:

An exponential model was chosen based on data fit and parsimony. A data set from a HIV challenge study using a nonhuman primate model and another data set from reported human blood transfusions associated with HIV infected donors were separately fit to the model to generate parameter estimates. A Bayesian framework using No-U-Turn Sampling (NUTS) and Monte Carlo simulations was performed to generate posterior distributions quantifying uncertainty in parameter estimation and model predictions.

Results:

The parameters of the exponential model for both nonhuman primate and human data were estimated with a mean (95% credible intervals) of 2.70 × 10−2 (7.74 × 10−3, 6.06 × 10−2) and 7.56 × 10−4 (3.68 × 10−4, 1.31 × 10−3), respectively. The predicted ID50 for the animal and human models was 26 (12, 90) and 918 (529, 1886) RNA copies transfused, respectively.

Conclusion:

This dose–response model can be used in a quantitative framework to estimate the probability of transfusion-transmission of HIV through WP donations. These models can be especially informative when assessing risk from blood components with low viral load.
Development and Validation of a Deep Learning System for the Diagnosis of Pediatric Diseases: A Large-Scale Real-World Data Study in Shanghai
Authors: Ge Xiaoling , Wang Yi , Xie Li , Shang Yujuan , Zhai Yihui , Huang Zhiheng , Huang Jianfeng , Ye Chengjie , Ma Ao , Li Wanting , Zhang Xiaobo , Xu Hong
Published: October 2022

Background

Artificial intelligence (AI)-assisted diagnosis is considered to be the future direction of improving the efficiency and accuracy of pediatric diseases diagnosis, while the existing research based on AI are far from sufficient because of limited data amount, inadequate coverage of disease types, or high construction costs, and have not been applied on a large scale. We aimed to develop an accurate deep learning model trained on millions of real-world data to verify the feasibility of the technology, and build the whole process of outpatient auxiliary diagnosis.

Methods and findings

We applied a Chinese Natural Language Processing (NLP) and an end-to-end deep neural network classifier to the outpatient’s electronic medical records (EMRs) in a single child care center in Shanghai, China, to unstructured text processing and construct an auxiliary diagnostic model, all patients were aged from 0 to 18 years. A training cohort with millions of records and an independent validation cohort with tens of thousands of records were intake separately and calculate diagnosis concordance rate (DCR) of model in each diseases group. The records with inconsistent diagnoses between human and AI were evaluated by clinical experts’ group, and calculate the relative correct rate (RCR) to evaluate the diagnostic performance of the model. A total of 5,271,347 medical records were intake in model training covering sixteen categories of diseases according to disease coding, reaching a DCR of 95· 49% (95· 48∼95· 51). For validation, 91,880 records were obtained from validation dataset, which reached a DCR of 93· 51% (93· 35∼93· 67) and FDCR of 72.04% (71· 75∼72· 33). It was confirmed that the accuracy of the model was still higher than that of human with most RCR>1 in validation dataset.

Conclusions

The deep learning system could support diagnosis of pediatric diseases, which has high diagnostic performance, comprehensive disease coverage, feasible technology, and can be promoted in multiple sites in the future.

Funding

The Authors received no specific funding for this work.
Integrated analysis of cell-free DNA for the early detection of cancer in people with Li-Fraumeni Syndrome
Authors: Wong Derek , Luo Ping , Oldfield Leslie , Gong Haifan , Brunga Ledia , Rabinowicz Ron , Subasri Vallijah , Chan Clarissa , Downs Tiana , Farncombe Kirsten M , Luu Beatrice , Norman Maia , Eagles Jenna , Pederson Stephenie , Wellum Johanna , Danesh Arnavaz , Prokopec Stephenie , Zhao Eric , Znassi Nadia , Lam Bernard , Marsh Kayla , Sundaravadanam Yogi , Torti Dax , Malkin David , Kim Raymond H , Pugh Trevor J
Published: October 2022

Despite advances in cancer therapeutics, early detection is often the best prognostic indicator for survival (1). People with Li-Fraumeni syndrome harbor a germline pathogenic variant in the tumor suppressor geneTP53(2) and face a near 100% lifetime risk of developing a wide spectrum of, often multiple, cancers (3).TP53mutation carriers routinely undergo intensive surveillance protocols which, although associated with significantly improved survival, are burdensome to both the patient and the health care system (4). Liquid biopsy, the analysis of cell-free DNA fragments in bodily fluids, has become an attractive tool for a range of clinical applications, including early cancer detection, because of its ability to provide real-time holistic insight into the cellular milieu (5). Here, we assess the efficacy of a multi-modal liquid biopsy assay that integrates a targeted gene panel, shallow whole genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a cohort of Li-Fraumeni syndrome patients: 196 blood samples from 89 patients, of which 26 were pediatric and 63 were adults. Our integrated analysis was able to detect a cancer-associated signal in 79.4% of samples from patients with active cancer, a 37.5% – 58.8% improvement over each individual analysis. Through analysis of patient plasma at cancer negative timepoints, we were able to detect cancer-associated signals up to 16 months prior to occurrence of cancer as detected by conventional clinical modalities in 17.6% ofTP53mutation carriers. This study provides a framework for the integration of liquid biopsy into current surveillance methods for patients with Li-Fraumeni syndrome.
Gut microbial disruption in critically ill patients with COVID-19 associated pulmonary aspergillosis
Authors: Maurer H. Carlo , Schult David , Koyumdzhieva Plamena , Reitmeier Sandra , Middelhoff Moritz , Rasch Sebastian , List Markus , Janssen Klaus-Peter , Steiger Katja , Protzer Ulrike , Schmid Roland M. , Neuhaus Klaus , Haller Dirk , Quante Michael , Lahmer Tobias
Published: October 2022

Objectives

COVID-19 disease can be exacerbated byAspergillussuperinfection (CAPA). The causes of CAPA are not yet fully understood. Recently, alterations in the gut microbiome have been associated with a complicating course and increasing severity of COVID-19 disease, most likely via immunological mechanisms. Aim of this study was to investigate a potential association between severe CAPA and alterations in the gut and bronchial microbiota.

Methods

We performed 16S rRNA gene amplicon sequencing of stool and bronchial samples from a total of 16 COVID-19 patients with CAPA and 26 patients without CAPA. All patients were admitted to the intensive care unit. Results were carefully tested for potential influences on the microbiome during hospitalization.

Results

We found that late in COVID-19 disease, CAPA patients exhibited a trend towards reduced gut microbial diversity. Furthermore, late stage CAPA disease showed an increased presence ofStaphylococcus epidermidisin the gut. This is not found in late non-CAPA cases or early disease. The analysis of bronchial samples did not show significant results.

Conclusions

This is the first study showing alterations in the gut microbiome accompany severe CAPA and possibly influence the host’s immunological response. In particular, an increase ofStaphylococcus epidermidisin the intestine could be of importance.

The composition of intestinal bacteria in severe CAPA disease is altered with an increase in Staphylococcus epidermidis in the gut. Alterations in the composition of intestinal bacteria in severe CAPA may indicate immunologic involvement of the gut in the disease.
LINC01184 is highly expressed and functions as a tumor-promotive factor in hepatocellular carcinoma
Authors: Zhang Qiangnu , Yan Lesen , Chen Jiaojuan , Liu Liping
Published: October 2022

The expression and function of LINC01184 in hepatocellular carcinoma are unknown. We analyzed the changes in LINC01184 expression in hepatocellular carcinoma using public data, and also analyzed the relationship between LINC01184 and patient prognosis. In vitro, we investigated the effect of LINC01184 on HCC cell growth using cell activity analysis, clone formation analysis, and regulatory death analysis. We also explored the effect of LINC01184 on HCC cell migration using transwell analysis and scratch assay. We found that LINC01184 was significantly highly expressed in hepatocellular carcinoma tissues. Patients with high LINC01184 levels had poorer overall survival and disease-free survival. knockdown of LINC01184 in HUH7 and PLC/PRF/5 cells inhibited cell proliferation and induced regulatory death. Down-regulation of LINC01184 also leads to a reduction in the migratory capacity of cells. In conclusion, LINC01184 may become a biomarker or a new therapeutic target for HCC.
Assessing the epidemic impact of protests during the COVID-19 pandemic
Authors: Hong Inho , Ferreira Leonardo N. , Rutherford Alex , Cebrian Manuel
Published: October 2022

Protests during the COVID-19 pandemic present a complex trade-off between democratic rights of freedom of assembly and an epidemic risk, and have created a need for careful assessment of protest-driven infections. Here, we build a coupled disease transmission model and assess the impact of protests on the COVID-19 spread in the continental US using a dataset of 4,121 protests and 1.66 million protesters between April and June of 2020. We find that protests in 2020 had limited effects, creating tens of additional daily cases country-wide, due to their small size. However, a simple scaling relation of protest-driven infections derived from our simulations reveals that very large protests with over millions of participants can significantly boost outbreaks and impact the healthcare system. In the worst-case scenario, very large protests can add over 20,000 daily cases and over 7,000 ICU admissions over the continental US. We hope our model can aid the policy rationale to maintain freedom of assembly in the current and future pandemics, while providing estimates for preparations for a healthcare surge in the worst-case setting.
Comparative efficacy of antiviral strategies targeting different stages of the viral life cycle: A viral quasispecies dynamics study
Authors: Lwin Pancy , Lewis Greyson R. , Das Moumita , Jones Barbara A.
Published: October 2022

While the COVID-19 pandemic continues to impact public health worldwide significantly, the use of antiviral drugs and therapies has dramatically reduced the instances of severe disease and death. More broadly, the unprecedented use of antivirals also provides hope for preventing and mitigating similar viral outbreaks in the future. Here we ask: What are the comparative impact of antiviral therapeutics targeting different stages of the viral lifecycle? How do antiviral therapeutics impact the viral population in the bloodstream, or in other words, the viral load in high and low-immunity individuals? To address these questions, we use a model of viral quasispecies dynamics to examine the efficacy of antiviral strategies targeting three critical aspects of the viral life cycle, fecundity, reproduction rate, or infection rate. We find a linear relationship of the viral load with the change in fecundity and a power law with the change in the reproduction rate of the virus, with the viral load decreasing as the fecundity and the reproduction rates are decreased. Interestingly, however, for antivirals that target the infection rate, the viral load changes non-monotonically with the change in infection rate; the viral population initially increases and then decreases as the infection rate is decreased. The initial increase is especially pronounced for individuals with low immunity. By examining the viral population inside cells for such cases, we found that the therapeutics are only effective in such individuals if they stop the infection process entirely. Otherwise, the viral population inside cells does not go extinct. Our results predict the effectiveness of different antiviral strategies for COVID-19 and similar viral diseases and provide insights into the susceptibility of individuals with low immunity to effects like long covid.
A TMT-based quantitative proteomics approach toward α-syn PFF associated Lewy Body Dementia (LBD) using α-syn PFF-injected mouse brain tissues
Authors: Akkentli Fatih , Jang In kyu , Choi Yoonseop , Yoo Dongyoon , Oh Eric Joon-Hun , Na Chan Hyun , Ha Shinwon , Kang Sung-Ung
Published: October 2022

The aggregation of α-synuclein in the nervous system leads to a class of neurodegenerative disorders termed α-synucleinopathies. A form of primary degenerative dementia called Lewy body dementia (LBD) often develops in the case these aggregations develop into intracellular inclusions called Lewy bodies (LB) and Lewy neurites (LN). Despite the high frequency of LBD, being the leading cause of dementia following Alzheimer’s disease (AD), there is relatively little information discovered about its pathological pathway or diagnostic criteria. In this report, we attempt to address such shortcomings via utilizing a proteomic approach to identify the proteomic changes following intrastriatal injection of α-synuclein preformed fibril (α-syn PFF). Through mass spectrometry, we have identified a total of 179 proteins that were either up- or down-regulated at different time points, with the four proteins – TPP3, RAB10, CAMK2A, and DYNLL1 – displaying the most significant changes throughout the timeframe. Further examining the modulated proteins with network-based enrichment analyses, we have found that 1) the most significantly associated neurodegenerative pathways were Parkinson’s (pV = 3.0e-16) and Huntington’s (pV = 1.9e-15) disease, and 2) the majority of molecular functions specific to the pathology only appeared at later time points. While these results do not expose a conclusive biomarker for LBD, they suggest a potential framework that may be utilized to diagnose and differentiate LBD pathology from other forms of dementia by focusing on the cortical proteomic changes which occur in a later time span.