bluuebunny/crossref_metadata_2025 huggingface dataset:
Parkinson’s disease updates: Addressing the pathophysiology, risk factors, genetics, diagnosis, along with the medical and surgical treatment
Authors: Prajjwal Priyadarshi , Flores Sanga Herson S , Acharya Kirtish , Tango Tamara , John Jobby , Rodriguez Rene S.C. , Dheyaa Marsool Marsool Mohammed , Sulaimanov Mukhamed , Ahmed Aneeqa , Hussin Omniat A.
Published: October 2023

After only Alzheimer’s disease (AD), Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. The incidence of this disease increases with age, especially for those above 70 years old. There are many risk factors that are well-established in the contribution to the development of PD, such as age, gender, ethnicity, rapid eye movement sleep disorder, high consumption of dairy products, traumatic brain injury, genetics, and pesticides/herbicides. Interestingly, smoking, consumption of caffeine, and physical activities are the protective factors of PD. A deficiency of dopamine in the substantia nigra of the brainstem is the main pathology. This, subsequently, alters the neurotransmitter, causing an imbalance between excitatory and inhibitory signals. In addition, genetics is also involved in the pathogenesis of the disease. As a result, patients exhibit characteristic motor symptoms such as tremors, stiffness, bradykinesia, and postural instability, along with non-motor symptoms, including dementia, urinary incontinence, sleeping disturbances, and orthostatic hypotension. PD may resemble other diseases; therefore, it is important to pay attention to the diagnosis criteria. Parkinson’s disease dementia can share common features with AD; this can include behavioral as well as psychiatric symptoms, in addition to the pathology being protein aggregate accumulation in the brain. For PD management, the administration of pharmacological treatment depends on the motor symptoms experienced by the patients. Non-pharmacological treatment plays a role as adjuvant therapy, while surgical management is indicated in chronic cases. This paper aims to review the etiology, risk factors, protective factors, pathophysiology, signs and symptoms, associated conditions, and management of PD.
Rare occurrence of hemoglobin Lepore variant in a Palestinian patient: a case report and brief literature review
Authors: Asees Mohammad Y. , Shrateh Oadi N. , Jobran Afnan W.M. , Assi Ayuob S.
Published: October 2023

Introduction:

In hemoglobinopathies, a basic lesion alters the rate of globin synthesis or the structure of the globin in healthy hemoglobin (Hb). Genetic instructions are used to synthesize the polypeptide chains that make up globin chains. The kind and extent of the structural aberration of the Hb molecule are closely related to the clinical features. Hematologically, the heterozygous form of the Lepore syndrome has a pattern resembling minor thalassemia, and electrophoretically, it is characterized by aberrant Hb Lepore fractions at a rate of 5–15% and a decreased percentage of HbA and mildly increased HbF. Clinically speaking, Hb Lepore heterozygotes patients are asymptomatic and resemble the clinical picture of patients with mild thalassemia.

Case Presentation:

A 28-year-old female came to our attention for assessment of generalized weakness and fatigue for a 4-month duration. Laboratory evaluation, including complete blood count, showed mild microcytic hypochromic anemia with parameters resembling the thalassemia trait. Iron profile studies were normal. Abdominal ultrasound showed mild splenomegaly. Hb electrophoresis was performed and showed an abnormal high-performance liquid chromatography pattern with an abnormal Hb band, mild elevated HbF, and mild reduction in HbA. The interpretation of the Hb electrophoresis curve suggested heterozygosity for beta chain variant Hb Lepore.

Discussion and Conclusion:

Hb Lepore is one of the structural Hb variants with a characteristic fusion gene between the delta and beta chains. Hematologically, the heterozygous form of the Lepore syndrome has a pattern resembling the thalassemia trait. In Palestine, the prevalence of Hb Lepore, either homozygous or homozygous state, is unknown.
Exploring the transformative role of drone technology in advancing healthcare delivery in Africa; a perspective
Authors: Olatunji Gbolahan , Isarinade Timilehin David , Emmanuel Kokori , Olatunji Doyin , Aderinto Nicholas
Published: October 2023

This perspective article delves into the transformative potential of drone technology in revolutionising healthcare delivery in Africa. The continent faces numerous challenges in providing timely and efficient medical services to its vast and diverse population, compounded by geographical barriers, inadequate infrastructure and limited access to medical facilities. Amidst these challenges, the integration of drone technology emerges as a promising solution, offering unprecedented opportunities to overcome longstanding obstacles and improve healthcare accessibility across Africa. Drawing from existing drone-based healthcare initiatives in Africa, the article explores various applications of drones in healthcare delivery. These encompass but are not limited to, delivering vaccines, medications, blood samples, diagnostic tools and medical personnel to remote locations in a timely and cost-effective manner. Furthermore, the paper examines the operational challenges and regulatory considerations in deploying drone technology for healthcare and the ethical implications surrounding privacy and security.
Comparison of abdominal depth with subcutaneous fat thickness in predicting surgical site infection among patients undergoing hepatopancreatobiliary surgery: a prospective observational study
Authors: Dahal Suman , Gyawali Sushil , Neupane Prashansha , Neupane Priyanka , Hamal Aliza , Verma Rupesh , Pachhai Prarthana , Khadka Rabi , Karki Badal , Khatiwada Raj D. , Kansakar Prasan B. S.
Published: October 2023

Introduction:

Surgical site infection (SSI) is a significant cause of postoperative morbidity resulting in an increased hospital stay and cost. Various measures have been used to predict SSI such as subcutaneous fat thickness (SCFT) and abdominal depth (AD) in case of abdominal surgeries. The objective of the study was to compare SCFT with AD to predict SSI in HPB surgeries.

Methods:

A prospective observational study was conducted from February 2020 to February 2021, which included 76 patients who underwent elective open hepatopancreatobiliary surgeries. SCFT and AD at the level of the umbilicus were measured preoperatively using the computed tomography abdomen. The occurrence of SSI was evaluated in correlation with SCFT and AD. SCFT and AD were compared using the receiver operating characteristic curve for prediction of SSI.

Results:

Twenty-five (32.3%) patients who underwent elective HPB surgeries developed SSI. 72% of the SSI were superficial. In multivariate analysis, only SCFT was associated with SSI, which was statistically significant. It was compared with AD using the receiver operating characteristic curve where SCFT proved to be better at predicting SSI (AUC=0.884) with cut-off =2.13 cm, sensitivity 84%, and specificity 86%), compared to AD with an AUC of 0.449.

Conclusion:

SSI is the common cause of increased morbidity following hepato-pancreato-biliary surgeries with risk factors including SCFT and AD. Approximately one-third of patient developed SSI, with most the common being superficial SSI. SCFT at the incision site was associated with an increased rate of SSI and the better predictor for SSI as compared with the AD.
Effects of combined use of intermittent theta burst stimulation and cognitive training on post-stroke cognitive impairment : a single-blind randomized controlled trial
Authors: Zhang Youmei , Chu Minmin , Zheng Yanjun , Zhang Feilan , Yu Hong , Ye Xiancong , Xie Hangkai , Chen Jing , Qian Zhiyong , Zeng Chao , Chen Weihai , Pei Zhongcai , Zhang Yue , Chen Jianer
Published: October 2023

Objective

Post-stroke cognitive impairment (PSCI) substantially affects patients’ quality of life. This study explored the therapeutic efficacy of intermittent theta burst stimulation (iTBS) combined with cognitive training for PSCI.

Design

The experimental group received iTBS and cognitive training, whereas the control group only received cognitive training, both for six weeks. The outcome measures were the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA), Modified Barthel Index (MBI), Transcranial Doppler Ultrasonography (TCD), and Functional Near-infrared Spectroscopy (fNIRS).

Results

After therapy, between-group comparisons revealed a substantial difference in the LOTCA scores (P = 0.024). Improvements in visuomotor organization and thinking operations were more noticeable in the experimental group than in the other groups (P = 0.017 and P = 0.044, respectively). After treatment, the resistance index of the experimental group differed from that of the control group; channels 29, 37, and 41 were activated(P < 0.05). The active locations were the left dorsolateral prefrontal cortex (DLPFC), prefrontal polar cortex, and left Broca’s region.

Conclusion

iTBS combined with cognitive training had a superior effect on improving cognitive function and everyday activities compared with cognitive training alone, notably in visuomotor organization and thinking operations. iTBS may enhance cognitive performance by improving network connectivity.
Clinician perspectives on postamputation pain assessment and rehabilitation interventions
Authors: Rich Tonya L. , Falbo Kierra J. , Phelan Hannah , Gravely Amy , Krebs Erin E. , Finn Jacob A. , Matsumoto Mary , Muschler Katherine , Olney Christine M. , Kiecker Jessica , Hansen Andrew H.
Published: October 2023

Objective:

The purpose of this study was to explore self-reported Veterans Affairs (VA) amputation clinician perspectives and clinical practices regarding the measurement and treatment for amputation-related pain.

Study Design:

Cross-sectional survey with 73 VA rehabilitation clinicians within the VA Health Care System.

Results:

The most frequent clinical backgrounds of respondents included physical therapists (36%), prosthetists (32%), and physical medicine and rehabilitation specialist (21%). Forty-one clinicians (56%) reported using pain outcome measures with a preference for average pain intensity numeric rating scale (generic) (97%), average phantom limb pain intensity numeric rating scale (80%), or Patient-Reported Outcomes Measurement Information System pain interference (12%) measures. Clinicians' most frequently recommended interventions were compression garments, desensitization, and physical therapy. Clinicians identified mindset, cognition, and motivation as factors that facilitate a patient's response to treatments. Conversely, clinicians identified poor adherence, lack of belief in interventions, and preference for traditional pain interventions (e.g., medications) as common barriers to improvement. We asked about the frequently used treatment of graded motor imagery. Although graded motor imagery was originally developed with 3 phases (limb laterality, explicit motor imagery, mirror therapy), clinicians reported primarily using explicit motor imagery and mirror therapy.

Results:

Most clinicians who use standardized pain measures prefer intensity ratings. Clinicians select pain interventions based on the patient's presentation. This work contributes to the understanding of factors influencing clinicians' treatment selection for nondrug interventions. Future work that includes qualitative components could further discern implementation barriers to amputation pain rehabilitation interventions for greater consistency in practice.
Predictive model for diagnostic yield of bone marrow examination in patients with HIV infection having fever of unknown origin
Authors: Noiperm Panarat , Saelue Pirun
Published: October 2023

Objective:

Bone marrow examination is valuable for identifying the cause of fever of unknown origin (FUO) in HIV-infected patients. Based on the outcomes of bone marrow examination of patients with FUO, we aimed to develop a predictive model for identifying the factors that can increase the diagnostic yield of bone marrow examination.

Design:

For this retrospective cohort study, we enrolled HIV-infected patients, aged more than 15 years and diagnosed with FUO, at Songklanakarind Hospital in Southern Thailand, between January 2009 and December 2019.

Methods:

Evaluations were based on bone marrow aspiration, biopsy, and culture; any missing data were imputed with regression imputation.

Results:

Among the final 108 included patients, 44 (40.74%) showed positive bone marrow results. The diagnoses mainly comprised histoplasmosis, penicilliosis, and tuberculosis. Bone marrow examination led to treatment modifications in approximately 33% patients. Platelet count less than 150 000 cells/μl, alkaline phosphatase (ALP) level at least 200 U/l, and no previous antibiotic treatment were significantly associated with higher diagnostic yields. The HIV bone marrow (HIVBM) model, comprising of spleen size, hematocrit (Hct), platelet count before bone marrow examination, ALP level at admission, and previous antibiotic treatment, was generated as a nomogram to predict the diagnostic yield of bone marrow examination in HIV-infected patients with FUO.

Conclusion:

The results of this study indicate that the HIVBM model can be used to predict the diagnostic yield of bone marrow examination, and therefore assist in clinical decision-making regarding bone marrow procedures, to be performed for identifying the origin of fever in HIV-infected patients.
18F-FDG PET/CT Findings in Waldenström Macroglobulinemia With Mesentery Involvement
Authors: Chen Xueqi , Chen Guoqian , Li Qian , Fu Zhanli
Published: October 2023

A 74-year-old man presented to the hospital complaining of weight loss, increasing fatigue, and blurred vision. The abdominal ultrasonography initially revealed a massive lesion in the mesentery, which was later confirmed by a contrast-enhanced CT scan. The 18F-FDG PET/CT scan showed a single, solitary hypermetabolic mass. The patient was finally diagnosed with Waldenström macroglobulinemia with mesentery involvement by the histopathological examination.
Vascularized Denervated Muscle Targets for Headache Surgery—Presentation and Surgical Management
Authors: Bhoopalam Myan , Colakoglu Salih , Tuffaha Sami H. , Reddy Sashank K.
Published: October 2023

Patients with substantial trauma to their occipital nerves and those with recurrent or persistent chronic headaches after occipital nerve decompression surgery require transection of their greater occipital and/or lesser occipital nerves to control debilitating pain. Current techniques, such as burying the transected nerve stump in nearby muscle, do not prevent neuroma formation, and more advanced techniques, such as targeted muscle reinnervation and regenerative peripheral nerve interface, have demonstrated only short-term anecdotal success in the context of headache surgery. Vascularized denervated muscle targets (VDMTs) are a novel technique to address the proximal nerve stump after nerve transection that has shown promise to improve chronic nerve pain and prevent neuroma formation. However, VDMTs have not been described in the context of headache surgery. Here authors describe the etiology, workup, and surgical management of 2 patients with recurrent occipital neuralgia who developed vexing neuromas after previous surgery and were successfully treated with VDMTs, remaining pain-free at 3-year follow-up.
CIRC_0085323 SILENCING INHIBITS TNF-Α-INDUCED NORMAL HUMAN COLONIC EPITHELIAL CELL INFLAMMATION AND APOPTOSIS THROUGH THE MIR-495-3P/TRAF3 AXIS
Authors: An Qi , Yang Shengsen , Tao Jianan , Yang Mengdi , Ma Zhenqi , Gao Qian , Wang Xuehong
Published: October 2023

Background: Previous data have suggested the involvement of circular RNA (circRNA) in ulcerative colitis (UC) development. However, the role and mechanism of circ_0085323 in UC occurrence have not been reported. Methods: Normal human colonic epithelial cells (NCM460) were treated with TNF-α to simulate UC-like cell inflammation and injury in vitro. The expression of circ_0085323, microRNA-495-3p (miR-495-3p), and TNF receptor–associated factor 3 (TRAF3) was detected by quantitative real-time polymerase chain reaction. Protein expression was checked by western blotting analysis. Cell viability, cell proliferation, and cell apoptosis were investigated by cell counting kit-8 assay, 5-ethynyl-29-deoxyuridine assay, and flow cytometry analysis, respectively. IL-1β, IL-6, and IL-8 production were analyzed by enzyme-linked immunosorbent assays. Lactate dehydrogenase activity was assessed by a lactate dehydrogenase activity detection assay. The interactions among circ_0085323, miR-495-3p, and TRAF3 were identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: Circ_0085323 was overexpressed in the colonic mucosal tissues of UC patients and TNF-α–stimulated NCM460 cells. Circ_0085323 knockdown relieved TNF-α–induced inhibitory effect on the proliferation of NCM460 cells and promoting effects on cell apoptosis and inflammation. Circ_0085323 acted as a miR-495-3p sponge, and the effects of circ_0085323 silencing on TNF-α–induced NCM460 cell injury were attenuated by decreasing miR-495-3p expression. TRAF3 was targeted by miR-495-3p, and circ_0085323 combined with miR-495-3p to regulate TRAF3. TRAF3 depletion not only alleviated TNF-α–induced NCM460 cell damage but also partially revoked the effect of circ_0085323 silencing combined with miR-495-3p depletion on TNF-α–induced NCM460 cell injury. Conclusions: Circ_0085323 knockdown ameliorated TNF-α–induced NCM460 cell injury by regulating the miR-495-3p/TRAF3 axis, which suggested that circ_0085323 might be a therapeutic target for UC.
From 6-wk Lungs to 6 y: Increasing the Donor Pool for Pediatric Lung Transplantation
Authors: Purmessur Rushmi , Spencer Helen , Onwuka Nkechi Bliss , Muthialu Nagarajan , Berman Marius
Published: October 2023

Background.

Lung transplantation in the pediatric population is a challenge. With the donor pool being so small and lungs from young donors rare and precious, every organ available needs to be utilized to its best potential.

Case.

Here, we describe the case of a 6-wk-old donor of double lungs to a 5-mo-old baby girl diagnosed with alveolar capillary dysplasia with misalignment of the pulmonary veins. The recipient is doing very well, 6 y after the transplant, now following normal growth.

Discussion.

The challenges facing pediatric cardiothoracic transplantation in terms of organ supply and demand are enormous.

Conclusions.

In this article, we discuss some of the issues around the shortage of organs and alternatives to increase the organ donor pool.
Collaborative learning of new information in older age: a systematic review
Authors: Wolfe Kelly , Crompton Catherine J. , Hoffman Paul , MacPherson Sarah E.
Published: October 2023

Ageing is accompanied by a multitude of changes in cognitive abilities, which in turn affect learning. Learning collaboratively may benefit older adults by negating some of these age-related changes. However, studies on collaborative learning in older age differ in their methodology and findings. This systematic review provides an overview of the current research on collaborative learning in older age, exploring what factors influence collaborative learning in this age group. The titles and abstracts of imported 6629 works were screened, as well as four works added manually, which resulted in 29 studies. These studies were conducted across five countries (Canada, United States, United Kingdom, Switzerland and Belgium) between 1993 and 2023. Most studies were quantitative with a non-randomized (
n
= 16) design. Of the 29 studies, almost all studied collaboration in pairs (
n
= 28). The results suggest that the benefits of collaborating in older age may depend on the type of learning material, that familiarity between partners does not affect learning, and that age differences appear to decrease or disappear when older adults are provided with adequate time or trials. In addition, this systematic review identifies several gaps in the literature that future research should investigate further. This study was preregistered prior to its commencement on 21 January 2022. The accepted Stage 1 manuscript, unchanged from the point of in-principle acceptance, may be viewed at
https://osf.io/tj4w7/
. The data and materials of this study can be found at
https://osf.io/8xvqf/
.
A fatal case of necrotizing fasciitis by Aeromonas jandaei
Authors: Anil Anjali , Kumar Mani Bhushan , Chauhan Sachin , Ray Pallab , Dahiya Divya , Angrup Archana
Published: October 2023

Introduction : Necrotizing soft tissue infections are associated with an extremely fulminating course, owing to its rapid destruction of tissue planes underlying the skin. Aeromonas associated monomicrobial NSTIs are usually associated with exposure to fresh water, via trauma, trivial abrasions or even reptile bites, particularly among agricultural workers and fish handlers. Albeit uncommon in incidence, urgent medical and surgical intervention is required once diagnosis is reached.
Case report : A 40-year-old male patient, known case of alcoholic liver disease, presented to the emergency department with pain and diffuse swelling of bilateral lower limbs, which quickly progressed to form blackish discolouration and blebs. Blood for preliminary haematological and biochemical investigations, as well as fluid draining from blebs was sent for microbiological investigation. The gram stain revealed occasional pus cells and gram-negative bacilli, pure growth in aerobic culture was identified as Aeromonasjandaei by Matrix-assisted laser desorption/ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). Patient was started on empirical antimicrobials, though lesions continued to progress and he ultimately succumbed within 24 hours of his hospital stay.
Conclusion : As appropriate antimicrobial therapy and early surgical intervention are required for management of the same, occupational exposure and the fulminant course should raise suspicion of likelihood of Aeromonas associated infections.
Cleaning Up Our Disinfectants: Usage of antimicrobial biocides in direct-to-consumer products in Australia
Authors: Nunez Charles , Bamert Rebecca , Lambert Karen , Short Francesca
Published: October 2023

In supermarkets and chemists worldwide, consumers are faced with an array of antimicrobial domestic cleaning and personal hygiene products purporting to kill germs and keep people safe. Many of these proven active ingredients (biocides) encourage the development of antimicrobial resistance (AMR) in microbes and microbial populations, in turn increasing the likelihood of AMR infections. In order to understand and address the selective pressure towards AMR posed by the unrestricted use of biocides, it is necessary to understand which biocides are most frequently found in consumer products and the current regulatory framework that governs their use. In this research we survey the biocidal active ingredients in the major categories of cleaning and personal care products available from supermarkets and pharmacies in Australia, and comment on the regulations that dictate how these products are tested and marketed. Benzalkonium chloride and ethanol were the two most prevalent antimicrobial biocides in this study, while triclosan, which is banned in several jurisdictions, was found in a small number of products. In Australia, many antimicrobial consumer products are regulated for efficacy and safety under the Therapeutic Goods Act, but the potential to drive microbial adaptation and AMR is not considered. Overall this survey underscores the broad use and light regulation of antimicrobial biocides in products available to the general public in Australia, and provides an information resource to inform further research and stewardship efforts.
Characterizing Acute Low Back Pain in a Community-Based Cohort
Authors: Burke Colleen , Taylor Kenneth A. , Fillipo Rebecca , George Steven Z. , Kapos Flavia P. , Danyluk Stephanie , Kingsbury Carla A. , Seebeck Kelley , Lewis Christopher E. , Ford Emily , Plez Cecilia , Kosinski Andrzej S. , Brown Michael C. , Goode Adam P.
Published: October 2023

Acute low back pain (LBP) is a common experience, however, the associated pain severity, pain frequency, and characteristics of individuals with acute LBP in community settings have yet to be well understood. In this manuscript, three acute LBP severity categorization definitions were used based on LBP frequency combined with either 1) pain impact frequency (impact-based) or 2) pain intensity (intensity-based), as well as LBP pain interference frequency (interference only-based) severity categories. The purpose of this manuscript is to describe and then compare these acute LBP severity groups in the following characteristics: 1) sociodemographic, 2) general and physical health, and 3) psychological. This cross-sectional study used baseline data from 131 community-based participants with acute LBP (<4 weeks duration before screening and ≥30 pain-free days before acute LBP onset). Descriptive associations were calculated as prevalence ratios for categorical variables and Hedges’gfor continuous variables. Our analyses identified several large associations for impact-based and intensity-based categories with global mental health, global physical health, STarT Back Screening Tool risk category, and general health. Larger associations were found with social constructs (racially and ethnically minoritized, performance of social roles, and isolation) when using the intensity-based versus impact-based categorization. The interference-based category did not capture as much variability between acute LBP severity categories. This study adds to the literature by providing standard ways to characterize community-based individuals experiencing acute LBP. The robust differences observed between these categorization approaches suggest that how we define acute LBP severity is consequential; these different approaches may be used to improve the early identification of factors potentially contributing to the development of chronic LBP.
Data Extraction for Evidence Synthesis Using a Large Language Model: A Proof-of-Concept Study
Authors: Gartlehner G , Kahwati L , Hilscher R , Thomas I , Kugley S , Crotty K , Viswanathan M , Nussbaumer-Streit B , Booth G , Erskine N , Konet A , Chew R
Published: October 2023

Data extraction is a crucial, yet labor-intensive and error-prone part of evidence synthesis. To date, efforts to harness machine learning for enhancing efficiency of the data extraction process have fallen short of achieving sufficient accuracy and usability. With the advent of Large Language Models (LLMs), new possibilities have emerged to increase efficiency and accuracy of data extraction for evidence synthesis. The objective of this proof-of-concept study was to assess the performance of an LLM (Claude 2) in extracting data elements from published studies, compared with human data extraction as employed in systematic reviews. Our analysis utilized a convenience sample of 10 English-language, open-access publications of randomized controlled trials included in a single systematic review. We selected 16 distinct types of data, posing varying degrees of difficulty (160 data elements across 10 studies). We used the browser version of Claude 2 to upload the portable document format of each publication and then prompted the model for each data element. Across 160 data elements, Claude 2 demonstrated an overall accuracy of 96.3% with a high test-retest reliability (replication 1: 96.9%; replication 2: 95.0% accuracy). Overall, Claude 2 made 6 errors on 160 data items. The most common errors (n=4) were missed data items. Importantly, Claude 2’s ease of use was high; it required no technical expertise or training data for effective operation. Based on findings of our proof-of-concept study, leveraging LLMs has the potential to substantially enhance the efficiency and accuracy of data extraction for evidence syntheses.
A comparison of Markov and mechanistic models for STH prevalence projections in the context of survey design
Authors: Eyre Max T. , Bulstra Caroline A. , Johnson Olatunji , de Vlas Sake J. , Diggle Peter J. , Fronterrè Claudio , Coffeng Luc E.
Published: October 2023

Globally, there are over one billion people infected with soil-transmitted helminths (STHs), mostly living in marginalised settings with inadequate sanitation in sub-Saharan Africa and Southeast Asia. The WHO recommends an integrated approach to STH morbidity control through improved access to sanitation and hygiene education, and the delivery of preventive chemotherapy (PC) to school age children delivered through schools. Progress of STH control programmes is currently estimated using a baseline (pre-PC) school-based prevalence survey and then monitored using periodical school-based prevalence surveys, known as Impact Assessment Surveys (IAS). We investigated whether integrating geostatistical methods with a Markov model or a mechanistic transmission model for projecting prevalence forward in time from baseline can improve IAS design strategies. To do this, we applied these two methods to prevalence data collected in Kenya, before evaluating and comparing their performance in accurately informing optimal survey design for a range of IAS sampling designs. We found that although both approaches performed well, the mechanistic method more accurately projected prevalence over time and provided more accurate information for guiding survey design. Both methods performed less well in areas with persistent STH hotspots where prevalence did not reduce despite multiple rounds of PC. Our findings show that these methods can be useful tools for more efficient and accurate targeting of PC. The general framework built in this paper can also be used for projecting prevalence and informing survey design for other NTDs.
From Sensory to Perceptual Manifolds: The Twist of Neural Geometry
Authors: Ma Heng , Jiang Longsheng , Liu Tao , Liu Jia
Published: October 2023

Classification constitutes a core cognitive challenge for both biological and artificial intelligence systems, with many tasks potentially reducible to classification problems. Here we investigated how the brain categorizes stimuli that are not linearly separable in the physical world by analyzing the geometry of neural manifolds in high-dimensional neural space, formed by macaques’ V2 neurons during a classification task on the orientations of motion-induced illusory contours. We identified two related but distinct neural manifolds in this high-dimensional neural space: the sensory and perceptual manifolds. The sensory manifold was embedded in a 3-D subspace defined by three stimulus features, where contour orientations remained linearly inseparable. However, through a series of geometric transformations equivalent to twist operations, this 3-D sensory manifold evolved into a 7-D perceptual manifold with four additional axes, enabling the linear separability of contour orientations. Both formal proof and computational modeling revealed that this dimension expansion was facilitated by nonlinear mixed selectivity neurons exhibiting heterogeneous response profiles. These findings provide insights into the mechanisms by which biological neural networks increase the dimensionality of representational spaces, illustrating how perception arises from sensation through the lens of neural geometry.
Controlling pericellular oxygen tension in cell culture reveals distinct breast cancer responses to low oxygen tensions
Authors: Rogers Zachary J. , Colombani Thibault , Khan Saad , Bhatt Khushbu , Nukovic Alexandra , Zhou Guanyu , Woolston Benjamin M. , Taylor Cormac T. , Gilkes Daniele M. , Slavov Nikolai , Bencherif Sidi A.
Published: October 2023

Oxygen (O2) tension plays a key role in tissue function and pathophysiology. O2-controlled cell culture, in which the O2concentration in an incubator’s gas phase is controlled, is an indispensable tool to study the role of O2in vivo. For this technique, it is presumed that the incubator setpoint is equal to the O2tension that cells experience (i.e., pericellular O2). We discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0.0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2consumption is the driving factor. RNA-seq revealed that primary human hepatocytes cultured in physioxia experience ischemia-reperfusion injury due to anoxic exposure followed by rapid reoxygenation. To better understand the relationship between incubator gas phase and pericellular O2tensions, we developed a reaction-diffusion model that predicts pericellular O2tensiona priori. This model revealed that the effect of cellular O2consumption is greatest in smaller volume culture vessels (e.g.,96-well plate). By controlling pericellular O2tension in cell culture, we discovered that MCF7 cells have stronger glycolytic and glutamine metabolism responses in anoxiavs.hypoxia. MCF7 also expressed higher levels ofHIF2A,CD73,NDUFA4L2,etc.and lower levels ofHIF1A,CA9,VEGFA, etc.in response to hypoxiavs.anoxia. Proteomics revealed that 4T1 cells had an upregulated epithelial-to-mesenchymal transition (EMT) response and downregulated reactive oxygen species (ROS) management, glycolysis, and fatty acid metabolism pathways in hypoxiavs.anoxia. Collectively, these results reveal that breast cancer cells respond non-monotonically to low O2, suggesting that anoxic cell culture is not suitable to model hypoxia. We demonstrate that controlling atmospheric O2tension in cell culture incubators is insufficient to control O2in cell culture and introduce the concept ofpericellular O2-controlled cell culture.
Comparing different methods of estimating GWAS heritability with a new approach using only summary statistics
Authors: Salehi Ehsan
Published: October 2023

So far SNP heritability (;variance explained by all SNP s used in genome-wide association study) has explained most of genetic variation for many traits but still there is a gap between GWAS heritability (; variance explained by genome-wide significant SNPs) andthat is named hidden heritability.

There are several methods for estimating(linear_mixed_model (LMM), PRS, multiple_linear_regression (MLR) and simple_linear_regression(SLR)). However, it is unclear which methods are more accurate under different circumstances. This study proposes a PRS based method for estimatingthat uses pseudo summary statistics. It compares this method with existing methods using both simulated and real data (10 traits from UKBB) to determine when they are realistic and can be trusted as a final estimate.

Simulation results showed that PRS-based methods underestimatenear 20% when considering all causal SNPs. But they are relatively accurate when using a subset of causal SNPs. Their performance is much better than SLR method for all 10 traits, although when applied to real data, they do not follow a stable trend of overestimation or underestimation compared to the base model (LMM).

My suggestion is to use LMM or adjusted_R2from MLR for reportingwhen an independent data set is available. In cases where only summary statistics is available, the PRS-PSS is relatively an accurate alternative, especially compared to SLR, which tends to overestimateby 20-50% when applying it on real data.
Colon cancer arises from differentiated cell lineages in the context of inflammation
Authors: Verhagen Mathijs P. , Joosten Rosalie , Schmitt Mark , Välimäki Niko , Sacchetti Andrea , Rajamäki Kristiina , Choi Jiahn , Procopio Paola , Silva Sara , van der Steen Berdine , van den Bosch Thierry P.P. , Seinstra Danielle , Doukas Michail , Augenlicht Leonard H. , Aaltonen Lauri A. , Fodde Riccardo
Published: October 2023

According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, was shown to suppress intestinal stemness. Here, we employed Paneth cells (PCs) as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation. Upon inflammation, PC-specificApcmutations led to intestinal tumors reminiscent not only of those arising in inflammatory bowel disease (IBD) patients but also of a larger fraction of sporadic colon cancers. The latter is likely due to the inflammatory consequences of Western-style dietary habits, the major colon cancer risk factor. Computational methods designed to predict the cell-of-origin of cancer confirmed that, in a substantial fraction of sporadic colon cancers the cells-of-origin are secretory lineages and not stem cells.

One-Sentence Summary

Secretory cell lineages trigger tumor formation in the context of the major etiologic colon cancer risk factors.
Nucleolin-RNA interaction modulates rotavirus replication
Authors: Hernández-Guzmán Jey , Arias Carlos F. , López Susana , Sandoval-Jaime Carlos
Published: October 2023

Rotavirus infection is a leading cause of gastroenteritis in children worldwide, the genome of this virus is composed of eleven segments of dsRNA packed in a triple-layered protein capsid. Here, we investigated the role of nucleolin, a protein with diverse RNA-binding domains, on rotavirus infection. Knocking down the expression of nucleolin in MA104 cells by RNA interference resulted in a remarkable 5-fold increase in the production of infectious rhesus rotavirus (RRV) progeny, accompanied by an elevated synthesis of viral mRNA and genome copies. Further analysis unveiled an interaction between rotavirus segment 10 (S10) and nucleolin, potentially mediated by G-quadruplex domains on the viral genome. To determine whether the nucleolin-RNA interaction regulates RRV replication, MA104 cells were transfected with AGRO100, a compound that forms G4 structures and selectively inhibits nucleolin-RNA interactions by blocking the RNA binding domains. Under these conditions, viral production increased by 1.54-fold, indicating the inhibitory role of nucleolin on the yield of infectious viral particles. Furthermore, G4 sequences were identified in all eleven RRV dsRNA segments, and transfection of oligonucleotides representing G4 sequences in RRV S10 induced a significant increase in viral production. These findings show that rotavirus replication is negatively regulated by nucleolin through direct interaction with the viral RNAs by sequences forming G4 structures.

Importance

Viruses rely on cellular proteins to carry on their replicative cycle. In the case of rotavirus, the involvement of cellular RNA-binding proteins during the replicative cycle is a poorly studied field. In this work, we demonstrate for the first time the interaction between nucleolin and viral RNA of rotavirus RRV. Nucleolin is a cellular protein that has a role in the metabolism of ribosomal rRNA, and ribosome biogenesis, which seems to have regulatory effects on the quantity of viral particles and viral RNA copies of rotavirus RRV. Our study adds a new component to the current model of rotavirus replication, where cellular proteins can have a negative regulation on rotavirus replication.
Inversions Can Accumulate Balanced Sexual Antagonism: Evidence from Simulations and Drosophila Experiments
Authors: McAllester Christopher S. , Pool John E.
Published: October 2023

Chromosomal inversion polymorphisms can be common, but the causes of their persistence are often unclear. We propose a model for the maintenance of inversion polymorphism, which requires that some variants contribute antagonistically to two phenotypes, one of which has negative frequency-dependent fitness. These conditions yield a form of frequency-dependent disruptive selection, favoring two predominant haplotypes segregating alleles that favor opposing antagonistic phenotypes. An inversion associated with one haplotype can reduce the fitness load incurred by generating recombinant offspring, reinforcing its linkage to the haplotype and enabling both haplotypes to accumulate more antagonistic variants than expected otherwise. We develop and apply a forward simulator to examine these dynamics under a tradeoff between survival and male display. These simulations indeed generate inversion-associated haplotypes with opposing sex-specific fitness effects. Antagonism strengthens with time, and can ultimately yield karyotypes at surprisingly predictable frequencies, with striking genotype frequency differences between sexes and between developmental stages. To test whether this model may contribute to well-studied yet enigmatic inversion polymorphisms inDrosophila melanogaster, we track inversion frequencies in laboratory crosses to test whether they influence male reproductive success or survival. We find that two of the four tested inversions show significant evidence for the tradeoff examined, withIn(3R)Kfavoring survival andIn(3L)Okfavoring male reproduction. In line with the apparent sex-specific fitness effects implied for both of those inversions,In(3L)Okwas also found to be less costly to the viability and/or longevity of males than females, whereasIn(3R)Kwas more beneficial to female survival. Based on this work, we expect that balancing selection on antagonistically pleiotropic traits may provide a significant and underappreciated contribution to the maintenance of natural inversion polymorphism.
Retrospective Analysis of Mobile Colistin Resistance and Plasmid-Mediated Quinolone Resistance Genes inEscherichia coli: China, 1993-2019
Authors: Wang Yujin , Sun Dewei , Xu Zhengzhong , Jiao Xin’an , Chen Xiang
Published: October 2023

Plasmid-mediated quinolone resistance (PMQR) genes and mobile colistin resistance (MCR) genes inEscherichia coli(E. coli) have shown an increasing prevalence in recent years. This rise is particularly notable in China and several Southeast Asian countries, representing a significant threat to public health. In the present study, we conducted a retrospective analysis of MCR genes (mcr-1,mcr-2,mcr-3,mcr-4, andmcr-5) and PMQR genes (qnrA,qnrB,qnrC,qnrD,qnrE1,qnrVC,qnrS,aac(6’)-Ib-cr,qepA, andoqxAB). From the 3,663E. coliisolates examined, 1,613 (44.0%) tested positive for PMQR genes, either individually or in combination. Meanwhile, 262 isolates (7.0%) carried MCR genes. Minimum inhibitory concentration (MIC) analyses of 17 antibiotics for the MCR gene-carrying strains revealed universal multidrug resistance. Resistance to polymyxin varied between 4 μg/mL and 64 μg/mL, with MIC50 and MIC90 values at 8 μg/mL and 16 μg/mL, respectively. Additionally, fluctuations in the detection rates of these resistant genes correlated with the introduction of antibiotic policies, host origin, temporal trends, and geographical distribution.

IMPORTANCE

Antimicrobial resistance (AMR) has emerged as a threat to global health and development, andE. coliresistance remains an ongoing clinical challenge. However, the efficacy of colistin and quinolones has been compromised by the presence of various MCR and PMQR genes. To elucidate the prevalence and distribution of MCR and PMQR genes inE. coliisolates, we analyzed 3,663E. coliisolates from 29 provinces in China from 1993 to 2019. The results show that 1,613 (44.0%) tested positive for PMQR genes, 262 isolates (7.0%) carried MCR genes. And MICs analyses of 17 antibiotics for the MCR gene-carrying strains revealed universal multidrug resistance. These indicated prohibiting or strictly curtailing antimicrobial use in animal or human is urgently needed to reduce the growing threat from AMR.
Selenocysteine tRNA methylation promotes oxidative stress resistance in melanoma metastasis
Authors: Nease Leona A. , Church Kellsey P. , Delclaux Ines , Murakami Shino , Astorkia Maider , Zerhouni Marwa , Cascio Graciela , Hughes Riley O. , Aguirre Kelsey N. , Zumbo Paul , Dow Lukas E. , Jaffrey Samie , Betel Doron , Piskounova Elena
Published: October 2023

Selenocysteine-containing proteins play a central role in redox homeostasis. Their translation is a highly regulated process, dependent upon two tRNASecisodecoders differing by a single 2’-O-ribose methylation, called Um34. We characterized FTSJ1 as the Um34 methyltransferase and show that its activity is required for efficient selenocysteine insertion at the UGA stop codon during translation. Specifically, Loss of Um34 leads to ribosomal stalling and decreased UGA recoding. FTSJ1-deficient cells are more sensitive to oxidative stress and have decreased metastatic colonization in xenograft models of melanoma metastasis. We found that FTSJ1 mediates efficient translation of selenoproteins essential for the cellular antioxidant response. Our findings uncover a role for tRNASecUm34 modification in oxidative stress resistance and highlight FTSJ1 as a potential therapeutic target specific for metastatic disease.
Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration
Authors: Buck Silas A. , Rubin Sophie A. , Kunkhyen Tenzin , Treiber Christoph D. , Xue Xiangning , Fenno Lief E. , Mabry Samuel J. , Sundar Varun R. , Yang Zilu , Shah Divia , Ketchesin Kyle D. , Becker-Krail Darius D. , Vasylieva Iaroslavna , Smith Megan C. , Weisel Florian J. , Wang Wenjia , Erickson-Oberg M. Quincy , O’Leary Emma I. , Aravind Eshan , Ramakrishnan Charu , Kim Yoon Seok , Wu Yanying , Quick Matthias , Coleman Jonathan A. , MacDonald William A. , Elbakri Rania , De Miranda Briana R. , Palladino Michael J. , McCabe Brian D. , Fish Kenneth N. , Seney Marianne L. , Rayport Stephen , Mingote Susana , Deisseroth Karl , Hnasko Thomas S. , Awatramani Rajeshwar , Watson Alan M. , Waddell Scott , Cheetham Claire E. J. , Logan Ryan W. , Freyberg Zachary
Published: October 2023

Parkinson’s disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 andDrosophilaortholog dVGLUT have been implicated as modulators of DA neuron resilience. However, the mechanisms by which VGLUT2/dVGLUT protects DA neurons remain unknown. We discovered DA neuron dVGLUT knockdown increased mitochondrial reactive oxygen species in a sexually dimorphic manner in response to depolarization or paraquat-induced stress, males being especially affected. DA neuron dVGLUT also reduced ATP biosynthetic burden during depolarization. RNA sequencing of VGLUT+DA neurons in mice and flies identified candidate genes that we functionally screened to further dissect VGLUT-mediated DA neuron resilience across PD models. We discovered transcription factors modulating dVGLUT-dependent DA neuroprotection and identified dj-1β as a regulator of sex-specific DA neuron dVGLUT expression. Overall, VGLUT protects DA neurons from PD-associated degeneration by maintaining mitochondrial health.