bluuebunny/crossref_metadata_2025 huggingface dataset:
Political Parties
Authors: Kailash K. K.
Published: September 2024

Political parties are central actors in representative democracies, and research on political parties is a key subfield of Indian politics. However, the organizational form that parties take in terms of its structure and relationships between different elements of the party has received little attention. This chapter attempts to explain the remarkable similarity in parties' organizational structure and functioning despite their origins in different times. While the impact of parties on the party system is well-studied, the effect of the party system on political parties has been ignored. The chapter tentatively concludes that the party system may explain the convergence of political parties towards a centralized electoral machine model.
Insurgencies and Political Violence in India
Authors: Staniland Paul
Published: September 2024

The heterogeneity of forms of conflict and the trajectories that violence can take in India is distinctive and important. Political violence in India includes numerous separatist insurgencies, a decades-long Maoist rebellion, armed political parties deeply embedded in mainstream electoral politics, local lynchings and vigilantism, and communal riots that are often linked to broader political trends. This is a remarkably diverse array of violence forms that make strong generalizations impossible. This chapter categorizes the types of violence and the different dynamics they can take on in order to put analytical structure on this complexity. It surveys a wide range of forms of conflict and then considers the role of violence in Indian politics.
Somatization differentiates fibromyalgia from low back pain: a comparative, cross-sectional cohort study
Authors: Angst Felix , Geiser Franziska , Benz Thomas , Lehmann Susanne , Sándor Peter S
Published: September 2024

Objectives

To examine whether somatization, depression, anxiety, fatigue, coping dimensions, pain, physical and social function, or sociodemographic characteristics can differentiate fibromyalgia from low back pain in a cross-sectional cohort setting of our Zurzach Interdisciplinary Pain Programme.

Methods

Fibromyalgia and low back pain (not fulfilling the diagnostic criteria for fibromyalgia) were compared using the Symptom Checklist-90R (SCL-90R) Somatization scale, the Quantification Inventory for Somatoform Syndromes (QUISS) Number of somatoform symptoms and other standardized instruments. Standardized mean differences (SMDs) quantified the score differences, and binomial logistic regression modelling with various covariates differentiated fibromyalgia from low back pain.

Results

The largest differences indicating worse health in fibromyalgia (n = 131) were in somatization (SCL-90R: SMD = −0.971, QUISS: SMD = −0.960), followed by affective health, pain and coping (SMDs between −0.632 and −0.280). Physical and social functioning were comparable in the two conditions (n = 262 low back pain). The two somatization scales both with odds ratios (OR) = 0.966 (P ≤ 0.002) plus female sex (OR = 3.396, P < 0.001) predicted 74.3% of the cases correctly (accuracy) with a positive predictive value of 65.3% and a specificity of 87.0% for fibromyalgia. In the female subsample (n = 280), the model remained stable with an accuracy of 71.9%.

Conclusion

Somatization stood out from all other somatic, psychosocial and coping dimensions and sociodemographics as the one significant specific predictor distinguishing fibromyalgia from low back pain. The fibromyalgia phenotype is characterized by the generalization of painful loci but equally prominently by generalized somatoform symptoms. Assessment of somatization is recommended to ensure accurate identification and understanding of the multifaceted syndrome of fibromyalgia.
The Battle of Endoscopic Bariatric Therapies for Obesity: Endoscopic Sleeve Gastroplasty Versus Endoscopically Inserted Intragastric Balloon—A Pairwise Meta-Analysis of Comparative Studies and a Call for Randomized Controlled Trials
Authors: Diab Abdul-Rahman F. , Sujka Joseph A. , Mattingly Kathleen , Sachdeva Mehak , Hackbarth Kenneth , Docimo Salvatore , DuCoin Christopher G.
Published: September 2024

Background:

Endoscopic sleeve gastroplasty (ESG) represents the latest primary endoscopic intervention for managing obesity. Both ESG and intragastric balloons (IGBs) have demonstrated effectiveness and safety for weight loss. However, there is a paucity of high-quality evidence supporting the superiority of one over the other, and no pairwise meta-analysis of comparative studies has been published to date. Our aim was to conduct a pairwise meta-analysis of comparative studies directly comparing ESG and IGB.

Methods:

We systematically conducted a literature search on PubMed and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search used specific search terms. The Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) Tool was used to evaluate the quality of the included studies. Data were analyzed using Review Manager (RevMan) 5.4.1 software with a random-effects model. The statistical method used was the Mantel-Haenszel method. For dichotomous data, the effect size was represented using odds ratio (OR), while mean difference (MD) was utilized as the effect size for continuous data.

Results:

After screening 967 records, a total of 9 studies met the inclusion criteria for this meta-analysis (5302 patients). The quality assessment categorized 5 studies as having a moderate risk of bias, while 3 studies were classified as having a low risk of bias. Sufficient information was not available for one study to ascertain its overall quality. A statistically significant increase in total weight loss percentage (TWL%) at 1 and 6 months was observed with ESG compared with IGB. In addition, a statistically insignificant decrease in the incidence of adverse events and readmissions was observed with ESG. Furthermore, a statistically significant decrease in the incidence of reintervention was observed with ESG.

Conclusions:

While this study suggests a higher TWL% associated with ESG compared with IGB, drawing definitive conclusions is challenging due to limitations identified during a comprehensive quality assessment of the available literature. We advocate for randomized controlled trials (RCTs) directly comparing the newer IGB (with a 12-mo placement duration) with ESG. However, this study consistently reveals higher rates of early reintervention (re-endoscopy) within the IGB group, primarily necessitated by the removal or adjustment of the IGB due to intolerance. Given the additional intervention required at 6 or 12 months to remove the temporarily placed IGB, this trend may imply that IGB is less economically viable than ESG. Cost-effectiveness analyses comparing ESG and IGB are warranted to provide valuable scientific insights.
Circulating Vesicular-bound HLA-G as Noninvasive Predictive Biomarker of CLAD After Lung Transplantation
Authors: Brugière Olivier , Dreyfuss Dora , Guilet Ronan , Rong Sophie , Hirschi Sandrine , Renaud-Picard Benjamin , Reynaud-Gaubert Martine , Coiffard Benjamin , Bunel Vincent , Messika Jonathan , Demant Xavier , Le Pavec Jérôme , Dauriat Gaelle , Saint Raymond Christel , Falque Loic , Mornex Jean-Francois , Tissot Adrien , Lair David , Le Borgne Krams Aurelie , Bousseau Veronique , Magnan Antoine , Picard Clément , Roux Antoine , Glorion Matthieu , Carmagnat Maryvonick , Gazeau Florence , Aubertin Kelly , Carosella Edgardo , Vallée Alexandre , Landais Cecile , Rouas-Freiss Nathalie , LeMaoult Joel ,   the COLT Consortium
Published: September 2024

Background.

Circulating extracellular vesicles (EVs) have shown promising results as noninvasive biomarkers for predicting disease outcomes in solid organ transplantation. Because in situ graft cell expression of the tolerogenic molecule HLA-G is associated with acceptance after lung transplantation (LTx), we hypothesized that plasma EV-bound HLA-G (HLA-GEV) levels could predict chronic lung allograft dysfunction (CLAD) development.

Methods.

We analyzed 78 LTx recipients from the Cohort-for-Lung-Transplantation cohort, all in a stable (STA) state within the first year post-LTx. At 3 y, 41 patients remained STA, and 37 had CLAD (bronchiolitis obliterans syndrome, BOS, [n = 32] or restrictive allograft syndrome [n = 5]). HLA-GEV plasma levels were measured at month 6 (M6) and M12 in 78 patients. CLAD occurrence and graft failure at 3 y post-LTx were assessed according to early HLA-GEV plasma levels.

Results.

In patients with subsequent BOS, (1) HLA-GEV levels at M12 were significantly lower than those in STA patients (P = 0.013) and (2) also significantly lower than their previous levels at M6 (P = 0.04).

A lower incidence of CLAD and BOS and higher graft survival at 3 y were observed in patients with high HLA-GEV plasma levels at M12 (high versus low HLA-GEVs patients [cutoff 21.3 ng/mL]: freedom from CLAD, P = 0.002; freedom from BOS, P < 0.001; and graft survival, P = 0.04, [log-rank]). Furthermore, in multivariate analyses, low HLA-GEV levels at M12 were independently associated with a subsequent risk of CLAD, BOS, and graft failure at 3 y (P = 0.015, P = 0.036, and P = 0.026, respectively [Cox models]).

Conclusions.

This exploratory study suggests the potential of EV-bound HLA-G plasma levels as a liquid biopsy in predicting CLAD/BOS onset and subsequent graft failure.
Quality characteristics and bread-making properties of Korean whole
wheat flour produced at different addition levels of wheat bran
Authors: Park Jeongmin , Yoon Sung Ran , Ryu Jung A
Published: September 2024

Whole wheat flour is produced by grinding wheat grains and blending each milling
fraction such as wheat bran and white flour with no specific standard for the
proportions. An exploration on classifying and utilizing Korean whole wheat
flour is required to increase the practical use of many different types of
Korean wheat flour products. This study aimed to examine factors for
categorization and processability of Korean whole wheat flour by investigating
quality characteristics and bread-making properties of Korean hard wheat flour
samples produced with different levels of wheat bran (0% as control,
5%, 10%, 15%, 20%, and whole grain wheat flour). The
ash content of flour samples was divided into six gradational categories, which
could be suggested as classification criteria for Korean whole wheat flour. The
main parameters of dough and gelatinization properties of the flour samples
exhibited downtrends, but nutritional constituents demonstrated uptrends with
increasing bran addition level. The bread specific volume, hardness, chewiness,
and brittleness of bread had strong correlations with dough stability and
pasting parameters, which could be presented as significant factors for
predicting bread-making properties of Korean whole wheat flour.
Effect of extracting solvents on physicochemical properties of
vegetable seed oils and their suitability for industrial
applications
Authors: Essien Qeency Etim , Akpe Michael Akomaye , Udo Ofonime Okon , Nwobodo Collins Irechukwu
Published: September 2024

The effects of extracting solvents on the physicochemical properties of vegetable
oils extracted from four oil seed plants, namely Dennettia
tripetala, Dacryodes edulis, Cola
rostrata, and Persea americana, were studied.
Vegetable oils were extracted using the Soxhlet method. The oils were used for
determining % yield, acid value (AV), iodine value (IV), saponification
value (SV), electrical conductivity (EC), and pH. The results revealed that the
range of the mean % yield of oils extracted using hexane, carbon
tetrachloride (CCl4), petroleum ether, acetone, and methanol,
respectively, were 7.5-12.0, 9.0-22.0, 7.5-27.5 and 12.0-37.5 for the four oil
Seeds respectively. Mean AVs of oils in mg KOH/g across the solvents were
3.1-3.7, 3.1-3.8, 2.5-3.9 and 2.4-2.8 for Cola rostrata,
Dacryodes edulis, Dennettia tripetala and
Persea americana respectively. Mean IVs of oils in
gI2/100 g across the solvents were 33.25-33.97, 33.06-33.35,
32.06-33.76 and 33.00-34.00 for the four oil seeds, respectively. Mean SVs in mg
KOH/g across the solvents were 191.00-197.44, 190.74-198.31, 194.11-202.52, and
182.23-199.44, respectively. Mean EC values ranged 0.31-0.32, 0.30-0.33,
0.30-0.33, and 0.31-0.32 μS/cm across the solvents, respectively. Mean pH
values ranged from 6.1-6.4, 4.6-6.3, 6.2-6.4, and 6.1-6.3 across the solvents
for the oils, respectively. The AVs of the oils suggest that they are edible
oils, the IVs classify the oils as non-drying oils suitable for paint making,
and SVs reveal that the oils are good for soap making. Hexane, petroleum ether,
and CCl4 are suitable for oil extraction industrially, while D.
edulis, D. tripetala, and P.
Americana oils are economically viable oil resources due to their
high percentage yield, SV and IV.
Comparison of essential oils and lignans compositions from pulp and
seed of Omija (Schisandra chinensis) berry
Authors: Kim Mi-Sun , Kwon Ye Seul , Choi Hyun Jin , Kim Young-Hoi , Choi Han-Seok
Published: September 2024

Fully ripe Omija (Schisandra chinensis Baillon)
berry has been used for medicinal and edible purposes for a long time due to its
various physiological activities. The seeds of Omija fruit are
produced during the processing of the fruit, but are often discarded in the food
industry. To increase the utilization of Omija seeds, this
study investigated the differences in essential oil and lignan compositions
between the pulp and seed. The yield of essential oil in whole berries was
1.33% based on dry weight, 0.91% in the pulp, and 2.65% in
the seed, respectively. A total of 62 constituents were identified by GC and
GC–MS analysis from the oils of the two parts. The major constituents were
sesquiterpenes, such as α-ylangene, cuparene, alloaromadendrene,
cis-lanceol, β-himachalene, and nootkatone. The content of these
ingredients was higher in the seed than in the pulp. The most abundant lignan
compounds in the berry were schizandrin, followed by γ-schizandrin,
schizandrin A, and schizandrol B. The content of the four lignans in the seed
was significantly higher than in the pulp. The seeds of Omija
have higher contents of essential oils and lignan compounds compared to the
pulp, making it necessary to explore approaches for utilizing them as food
ingredients.
Physiochemical properties and anti-proliferative activity against
human lung cancer cells of kombucha using sugar extracts of
Cudrania tricuspidata fruits
Authors: Cho MiAe , Song Kyoung Ju , Lee Jinwook , Lee Chang Moo , Choi Ho Chil , Park Jong Cheol
Published: September 2024

This study was conducted to develop kombucha with better
functionality. The developed kombucha (CK) was prepared using
the sugar extracts from fruits of Cudrania tricuspidata
(Carrière) Bureau ex Lavallée instead of the sugar, which is used
as a substrate for SCOBY in conventional kombucha (K). During
fermentation, the soluble solids content significantly decreased in CK compared
to K, and the pH change decreased rapidly in CK compared to K. On the
14th day of fermentation, the weight of the SCOBY in CK was
higher than that in K. Immediately after preparation, K contained only sucrose,
but CK contained sucrose, glucose, and fructose. SCOBY appears to use glucose
and fructose preferentially during fermentation. K contained acetic acid and
citric acid right after preparation. However, as fermentation progressed, the
composition changed to acetic acid, citric acid, and lactic acid. At the same
time, CK initially consisted of citric acid, lactic acid, and acetic acid.
However, acetic acid and citric acid increased but lactic acid decreased
significantly on the 14th day of fermentation. In the cytotoxicity
studies, the CK showed a proliferation-promoting effect on normal lung cells
(MRC-5) and strong cytotoxicity against human lung cancer cells (A549). These
results suggest that the kombucha made from sugar extracts of
C. tricuspidata fruits can be used as a more functional
beverage than regular kombucha.
Nutritional components and physiological activities of
kombucha containing ginseng sprouts
Authors: Lee Hee Yul , Lee Ga Young , Cho Kye Man , Joo Ok Soo
Published: September 2024

In this study, the physicochemical properties, nutritional components, and
antioxidant activities of kombucha containing ginseng sprouts
(control kombucha, CT; strawberry kombucha, ST
; strawberry kombucha with 2% ginseng sprout, ST+GS) were
analyzed for comparison of quality characteristics. The total content of free
amino acids in ST+GS (273.38 mg/100 mL) was 3.2-14.5 times higher than in CT
(18.9 mg/100 mL) and ST (84.9 mg/100 mL). The total mineral content in ST+GS
(63.99 mg/100 mL) was 3.3-4.1 times higher than those of CT and ST (15.45 and
19.28 mg/100 mL). The contents of soluble phenolic and soluble flavonoid were
1.2 mg GAE/mL and 0.14 mg RE/mL in ST+GS. Several ginsenosides were detected
only in ST+GS; ginsenoside Rg2 (2.4 mg/100 mL), Rh1 (4.5 mg/100 mL), F2 (9.0
mg/100 mL), Rg3 (4.6 mg/100 mL), and compound K (7.8 mg/100 mL) were detected.
The content of phenolic acids was 1.2-1.5 times higher in ST+GS than in CT and
ST. The amount of flavonol of ST+GS was not significantly different from CT but
was 1.4 times higher than in ST. In terms of antioxidant activities, the values
of ST+GS were significantly higher in comparison to other
kombucha samples. These results confirmed that
incorporating ginseng sprouts amplifies the advantages of
kombucha.
YTHDF1 Facilitates Lung Adenocarcinoma Progression via Promotion of EEF1G Translation in a m6A-Dependent Manner
Authors: Wang Lihong , Sheng Qihong , Wang Xiaoyu , Yue Hongjuan , Wang Qian , Zhang Mei , Ma Junling , Wu Ling , Zhang Jiaojiao , Cheng Zishuo , Yu Weifang , Liu Ting , Wang Jia
Published: September 2024

Lung adenocarcinoma (LUAD) is a malignant tumor with high morbidity and mortality worldwide, and overall survival rates for LUAD patients remain unimproved. RNA modification is a key process in post-transcriptional gene regulation in epigenetics, with N6-methyladenosine (m6A) being a common RNA modification. The molecular mechanisms of LUAD are unclear, but evidence suggests that m6A RNA methylation plays a significant role. This study aimed to clarify the role of YTHDF1 in LUAD development and pathogenesis. These findings confirmed that YTHDF1, a m6A reader protein, is highly expressed in LUAD tissues and is correlated with tumor differentiation and TNM stage. The results of functional loss experiments in LUAD cell lines revealed that downregulating YTHDF1 inhibits proliferation, migration, and invasion and induces apoptosis, with opposite effects observed upon YTHDF1 upregulation.In vivo, YTHDF1 knockout suppressed LUAD xenograft growth. RNA-seq, MeRIP-seq, RIP-seq, and bioinformatics analyses identified EEF1G as a downstream target of YTHDF1 in LUAD, and high expression of EEF1G was confirmed. The interaction between YTHDF1 and EEF1G was validated through RIP-qPCR, Co-IP and Co-IF assays. The overexpression of EEF1G in LUAD cells partially counteracts the tumor suppression induced by YTHDF1 silencing, and the knockdown of EEF1G has the opposite effect, further confirming the regulatory relationship. In summary, this study describes a novel YTHDF1/EEF1G regulatory pathway in which YTHDF1 promotes LUAD progression by recognizing and binding to the m6A-modified mRNA of EEF1G, accelerating its translation, suggesting that YTHDF1 may be a potential biomarker and therapeutic target.
AyurPhenoClusters define common molecular roots for rare diseases and uncover ciliary dysfunctions in syndromic conditions
Authors: Joshi Aditi , Jangir Deepika , Sharma Ashish , Anand Tanay , Verma Hamendra , Manvi  , Rangani Nupur , Joshi Pallavi , Singh Ravi Pratap , Kumar Sandeep , Girdhar Shipra , Sharma Rakesh , Kumar Abhimanyu , Dey Lipika , Mukerji Mitali
Published: September 2024

Managing rare genetic diseases with organ centric focus presents a challenge in linking genotypes to phenotypic traits. Ayurveda on the other hand, diagnose diseases with multisystem perspective that are assessed by perturbations along three physiological dimensions viz-kinetic (Vata), metabolic (Pitta) and structural (Kapha) each with distinct phenotypic attributes and molecular correlates. This study explores how rare diseases can be viewed from an Ayurvedic perspective by unifying the medical terminologies from both disciplines through Human Phenotype Ontology (HPO). Domain experts categorized 10,610 HPO terms into phenotypic groups based on Ayurvedic principles of Vata (V), Pitta (P), and Kapha (K) and used the Expectation Maximization (EM) algorithm to cluster and analyze 12,678 diseases. This revealed six distinct clusters collectively called “AyurPhenoClusters”. 2814 diseases had unique memberships to single clusters showing enrichment for V/P/K phenotypes. Clusterwise functional annotation revealed the top processes as (i) embryogenesis and skeletal system, morphogenesis; (ii) endocrine and ciliary functions (iii) DNA damage response and cell cycle regulation (iv) inflammation and immune response (v) immune, hemopoiesis, telomere aging (vi) Small molecule metabolism and transport. Most noteworthy, the K predominant cluster was significantly enriched for ciliary genes (43%) followed by a V predominant cluster (16 %). Our study also suggests that many rare diseases especially in the V cluster could be potential ciliopathies. This first of its kind of study provides an innovative framework that can bridge the gap between Ayurveda and modern medicine for improved mechanistic understanding of the rare diseases and pave the way for improved diagnostic and therapeutic strategies.

Significance Statement

Rare diseases, with an estimated global average of affecting 1 in 2500 persons, pose a substantial economic problem with frequent hospitalizations and expensive treatments. This study unifies Ayurvedabased principles with human phenotype ontologies to provide an innovative framework for understanding rare diseases. The study reveals six clusters of rare diseases with shared phenotypes and distinct molecular endophenotypes. Genes of two of the phenotypically distinct clusters converge to networks associated with ciliary dysfunctions highlighting the merit of this approach not only in identifying but endo-phenotyping ciliopathies. This offers new avenues for diagnosis, treatment, and drug repurposing and opens the possibility of adopting a system based holistic approach for reducing burden and improving quality of life.
Zika virus NS3 drives the assembly of a viroplasm-like structure
Authors: Sultana Tania , Zheng Chunfeng , Morton Garret , Megraw Timothy L.
Published: September 2024

Zika virus (ZIKV) is a mosquito-transmitted flavivirus that caused an epidemic in 2015-2016 in the Americas and raised serious global health concerns due to its association with congenital brain developmental defects in infected pregnancies. Upon infection, ZIKV assembles virus particles in a virus-generated toroidal compartment next to the nucleus called the replication factory, or viroplasm, which forms by remodeling the host cell endoplasmic reticulum (ER). How the viral proteins control viroplasm assembly remains unknown. Here we show that the ZIKV non-structural protein 3 (NS3) is sufficient to drive the assembly of a viroplasm-like structure (VLS) in human cells. NS3 encodes a dual-function protease and RNA helicase. The VLS is similar to the ZIKV viroplasm in its assembly near centrosomes at the nuclear periphery, its deformation of the nuclear membrane, its recruitment of ER, Golgi, and dsRNA, and its association with microtubules at its surface. While sufficient to generate a VLS, NS3 is less efficient in several aspects compared to viroplasm formation upon ZIKV infection. We further show that the helicase domain and not the protease domain is required for optimal VLS assembly and dsRNA recruitment. Overall, this work advances our understanding of the mechanism of viroplasm assembly by ZIKV and likely will extend to other flaviviruses.

Importance

The Zika virus replicates its genome and assembles virus particles in the cytoplasm within the replication organelle, a large virus-induced compartment also called the viroplasm. It does this in part by remodeling the endoplasmic reticulum. However, how the virus directs the host cell to assemble the viroplasm is mostly unknown. This study shows that Zika virus non-structural protein 3 (NS3) is sufficient to assemble a viroplasm-like structures, and indicates that NS3 has a central role in assembling the viroplasm. Understanding how the virus assembles the viroplasm compartment and NS3’s role in it should significantly advance our understanding of the cellular mechanisms of virus infection. This study aims to gain more understanding of the Zika virus and its viroplasm along with the molecular mechanisms for viroplasm assembly which might be shared by other viruses.
Supporting decision-making for individuals living with dementia and their care partners with knowledge translation: an umbrella review
Authors: Biard Marie , Detcheverry Flavie E. , Betzner William , Becker Sara , Grewal Karl S. , Azab Sandi , Bloniasz Patrick F. , Mazerolle Erin L. , Phelps Jolene , Smith Eric E. , Badhwar AmanPreet
Published: September 2024

Living with dementia requires decision-making about numerous topics including daily activities, such as advance care planning (ACP). Both individuals living with dementia and care partners require informed support for decision-making. We conducted an umbrella review to assess knowledge translation (KT) interventions supporting decision-making for individuals living with dementia and their informal care partners. Four databases were searched using 50 different search-terms, identifying 22 reviews presenting 32 KT interventions. The most common KT decision topic was ACP (N=21) which includes advanced care directives, feeding options, and placement in long-term care. The majority of KT interventions targeted care partners only (N=16), or both care partners and individuals living with dementia (N=13), with fewer interventions (N=3) targeting individuals living with dementia. Overall, our umbrella review offers insights into the beneficial impacts of KT interventions, such as increased knowledge and confidence, and decreased decisional conflicts.
A Comparison between Evidence-Generated Transtibial Sockets and Conventional Computer-Aided Designs, from the Patient’s Perspective
Authors: Mbithi Florence , Donovan-Hall Maggie , Bramley Jenny , Steer Joshua , Rossides Charalambos , Worsley Peter , Ostler Chantel , Metcalf Cheryl , Hannett Dominic , Ward Caroline , Kitchen Jack , Steventon Sioned , McIntosh Katy , Guo Shigong , Harvey Helen , Slater David Henderson , Kolli Vijay , Dickinson Alex
Published: September 2024

Objective

Personalised prosthetic socket design depends upon skilled prosthetists who aim to balance functional human-prosthesis coupling with safe, comfortable load transmission to skin and soft tissues. This study’s objective was to assess the comfort of sockets generated from past computer aided socket design records.

Design

A crossover non-inferiority trial with embedded qualitative interview study.

Setting

Three United Kingdom National Health Service clinics.

Participants

Seventeen people with nineteen transtibial amputations.

Intervention

Evidence-Generated sockets and conventional clinician-led computer aided (Control) designs

Main Measures

Socket Comfort Score and semi-structured interview.

Results

Evidence-Generated sockets had no statistically-significant difference in comfort compared to clinician-led Control sockets (p=0.38, effect size=0.08), but a lower socket comfort score variability across the group. Analysis of interviews revealed themes around fitting session experiences, similarities and differences between the Evidence-Generated and Control sockets, and residual limb factors impacting perceptions of socket comfort. These provided insights into the participants’ experience of the study and the value of expert prosthetist input in socket design.

Conclusions

Evidence-Generated sockets demonstrated noninferiority to conventional clinical computer aided design practice in terms of socket comfort. Both quantitative and qualitative results indicated how clinician input remains essential and is valued by prosthesis users. Work is underway to incorporate the evidence-generated sockets into computer aided design software such that they can act as a digital starting point for modification by expert clinicians at fitting, potentially reducing time spent on basic design, enabling prosthetists to focus on more highly-skilled customisation and co-design with their patients.
Employment Trajectories During the Menopause Transition: Experiences of Women with Early and Surgical Menopause
Authors: Peycheva Darina , Wielgoszewska Bozena , Zaninotto Paola , Steptoe Andrew , Hardy Rebecca
Published: September 2024

This study examines the labour market trajectories of women experiencing early and surgical menopause over a 10-year period surrounding their final menstruation or surgery, representing for most women the menopause transition. We also investigate the potential mediating role of hormone therapy (HT) in early postmenopause (within 5 years of menopause onset or surgery) in these relationships. Using data from the English Longitudinal Study of Aging (ELSA), we employ sequence and cluster analysis, followed by mediation analysis. Our findings indicate that women with early menopause, compared to those who undergo menopause at 45 or older, are less likely to have flexible working arrangements (part-time work or self-employment) compared to full-time work during this sensitive period. However, they are equally likely to exit the labour market as to work full-time, indicating distinct experiences. Surgical menopause, compared to natural menopause, is associated with an increased risk of labour market exit, particularly for women aged 45 or older at the time of surgery, potentially due to higher comorbidities and increased age-related precarity. HT use appears to mitigate the risk of labour market exit for women with both early and surgical menopause, although other factors (e.g., health) may play a more significant role in this transition out of work. We advocate for further research on the impact of early and surgical menopause on women’s labour market circumstances and for workplace policies that consider the diverse experiences of women with early and surgical menopause, including their increased risk of chronic conditions.
Effectiveness of Therapies Treating Sensory Processing Disorders in Children with Autism Spectrum Disorder
Authors: Orgel Joshua
Published: September 2024

The prevalence of children being diagnosed with Autism Spectrum Disorder has risen dramatically over recent years. Many of those children suffer from sensory processing disorders (SPD). There is no standardized treatment for this disorder and the therapies available have produced confusing and conflicting results. A search was performed for relevant studies and systematic review articles that researched treatment in this area. Data was extracted and analyzed and then organized with summary conclusions of each paper. Qualitative notes were gathered on the studies and the results of the studies were compared and contrasted. Sensory integration therapy has been shown to produce significant results and most of the conflicting data can be explained scientifically. Research is still required for the duration frequency and rate of therapy. Reviews of other therapies to treat SPD have not shown enough evidence of significant positive outcomes to be recommended.

Purpose Statement

The purpose of this paper is to gather and analyze research regarding therapies for Sensory Processing Disorder in Children with Autism Spectrum Disorder. This review aims to determine the evidence of such therapies and to inform and educate practitioners regarding outcomes in their use to treat this disorder.
Subtyping First-Episode Psychosis based on Longitudinal Symptom Trajectories Using Machine Learning
Authors: Liu Yanan , Jalali Sara , Joober Ridha , Lepage Martin , Iyer Srividya , Shah Jai , Benrimoh David
Published: September 2024

Clinical course after first episode psychosis (FEP) is heterogeneous. Subgrouping longitudinal symptom trajectories after FEP would be useful for developing personalized treatment approaches, and being able to predict these trajectories at baseline would facilitate individual-level treatment planning. We utilized k-means clustering to identify distinct clusters of 411 FEP patients based on longitudinal positive and negative symptom patterns. Ridge logistic regression was then used to identify predictors of cluster membership using baseline data. Three clusters were identified, demonstrating unique demographic, clinical and treatment response profiles. Cluster 1 exhibits lower positive and negative symptoms (LS), lower antipsychotic dose, and relatively higher affective psychosis; Cluster 2 shows lower positive symptoms, persistent negative symptoms (LPPN), and intermediate antipsychotic doses; Cluster 3 presents persistently high levels of both positive and negative symptoms (PPNS), as well as higher antipsychotic doses. We effectively predicted patients’ cluster membership (AUC of 0.74). The most important predictive features included contrasting trends of apathy, affective flattening, and anhedonia for the LS and LPPN clusters. Global hallucination severity, positive thought disorder and manic hostility predicted PPNS. These results help parse the heterogeneity of FEP trajectories and may facilitate the development of personalized treatment approaches tailored to cluster characteristics.
A Two-step Bayesian Mendelian Randomization Study on Cholecystitis and Dermatitis
Authors: Zhao Chenyu , Cen Changqian , Zhang Ruihan , He Wenjin , Jiao Yiyang , Chen Zhuoya , Wu Zhaoqi , Luan Ting
Published: September 2024

Background

Cholecystitis is an inflammatory disease involving the gallbladder, often associated with digestive disorders and systemic immune response. This systemic immune response could potentially influence the immune status of the skin, particularly in conditions like dermatitis. Despite extensive research on dermatitis, the causal relationship between cholecystitis and dermatitis subtypes (DSs) remains unclear.

Objective

The aim of this study was to investigate the causal relationship between cholecystitis and DSs.

Methods

Two-sample Mendelian randomization (MR) was used to analyze the causal relationship between cholecystitis and DSs. We then utilized the Bayesian Weighted Mendelian Randomization (BWMR) method to validate our findings and applied bidirectional MR analysis to confirm the causal direction. After establishing the associations between traits, we delved into the underlying mechanisms of this interesting finding. Subsequently, we used 91 inflammatory proteins as mediators and performed summary data-based mendelian randomization (SMR) analysis to further investigate the pathogenesis of DSs.

Results

MR results evidently showed that cholecystitis can significantly reduce the risk of allergic contact dermatitis (ACD) (IVW, OR=0.8834, p=0.0368) and exfoliative dermatitis (ED) (IVW, OR=0.5738, p=0.0126). BWMR also provided secondary validation of the casual associations. In the subsequent reverse direction MR analyses, reverse causality was not present, so cholecystitis had a unidirectional effect and existed as a protective factor for ACD and ED. Interestingly, cholecystitis appears to lower the risk of ACD and ED by downregulating IL-6, IL-7, and IFN-γ. Additionally, the genes HCG27 and HLA-DRB5 may play a significant role in the pathogenesis of ACD.

Conclusion

This study used a two-step MR analysis of genetic summary data to investigate to what extent inflammatory proteins impact the protective role of cholecystitis on dermatitis. We also identified several proteins and genes that could serve as potential drug targets.

Graphical abstract
Cap-independent translation directs stress-induced differentiation of the protozoan parasiteToxoplasma gondii
Authors: Dey Vishakha , Holmes Michael J. , Bastos Matheus S. , Wek Ronald C. , Sullivan William J.
Published: September 2024

Translational control mechanisms modulate microbial latency of eukaryotic pathogens, enabling them to evade immunity and drug treatments. The protozoan parasiteToxoplasma gondiipersists in hosts by differentiating from proliferative tachyzoites to latent bradyzoites, which are housed inside tissue cysts. Transcriptional changes facilitating bradyzoite conversion are mediated by a Myb domain transcription factor called BFD1, whose mRNA is present in tachyzoites but not translated into protein until stress is applied to induce differentiation. We addressed the mechanisms by which translational control drives BFD1 synthesis in response to stress-induced parasite differentiation. Using biochemical and molecular approaches, we show that the 5’-leader ofBFD1mRNA is sufficient for preferential translation upon stress. The translational control ofBFD1mRNA is maintained when ribosome assembly near its 5’-cap is impaired by insertion of a 5’-proximal stem-loop and upon knockdown of theToxoplasmacap-binding protein, eIF4E1. Moreover, we show that atrans-acting RNA-binding protein called BFD2/ROCY1 is necessary for cap-independent translation ofBFD1through its binding to the 5’-leader. Translation ofBFD2mRNA is also suggested to be preferentially induced under stress, but by a cap-dependent mechanism. These results show that translational control and differentiation inToxoplasmaproceed through cap-independent mechanisms in addition to canonical cap-dependent translation. Our identification of cap-independent translation in protozoa underscores the antiquity of this mode of gene regulation in cellular evolution and its central role in stress-induced life-cycle events.
Optical Neuroimage Studio (OptiNiSt): intuitive, scalable, extendable framework for optical neuroimage data analysis
Authors: Yamane Yukako , Li Yuzhe , Matsumoto Keita , Kanai Ryota , Desforges Miles , Gutierrez Carlos Enrique , Doya Kenji
Published: September 2024

Advancements in calcium indicators and optical techniques have made optical neural recording a common tool in neuroscience. As the volume of optical neural recording data grows, streamlining the data analysis pipelines for image preprocessing, signal extraction, and subsequent neural activity analyses becomes essential. There are a number of challenges in optical neural data analysis. 1) The quality of original and processed data needs to be carefully examined at each step. 2) As there are numerous image preprocessing, cell extraction, and activity analysis algorithms, each with pros and cons, experimenters need to implement or install them to compare and select optimal methods and parameters for each step of processing. 3) To ensure the reproducibility of the research, each analysis step needs to be recorded in a systematic way. 4) For data sharing and meta-analyses, adoption of standard data formats and processing protocols is required. To address these challenges, we developed Optical Neuroimage Studio (OptiNiSt) (https://github.com/oist/optinist), a framework for intuitively creating calcium data analysis pipelines that are scalable, extendable, and reproducible. OptiNiSt includes the following features. 1) Researchers can easily create analysis pipelines by selecting multiple processing modules, tuning their parameters, and visualizing the results at each step through a graphic user interface in a web browser. 2) In addition to common analytical tools that are pre-installed, new analysis algorithms in Python can be easily added. 3) Once a processing pipeline is designed, the entire workflow with its modules and parameters are stored in a YAML file, which makes the pipeline reproducible and deployable on high-performance computing clusters. 4) OptiNiSt can read image data in a variety of file formats and store the analysis results in NWB (Neurodata Without Borders), a standard data format for data sharing. We expect that this framework will be helpful in standardizing optical neural data analysis protocols.
Leveraging large language models for systematic reviewing: A case study using HIV medication adherence research
Authors: Lessani M. Naser , Li Zhenlong , Qiao Shan , Ning Huan , Aggarwal Abhishek , Yuan Guangzhe (Frank) , Pasha Atena , Stirratt Michael , Scott-Sheldon Lori A. J.
Published: September 2024

Background

The rapidly accumulating scientific literature in HIV presents a significant challenge in accurately and efficiently assessing the relevant literature. This study explores the potential capabilities of using large language models (LLMs), such as ChatGPT, for selecting relevant studies for a systematic review.

Method

Scientific papers were initially obtained from bibliographic database searches using a Boolean search strategy with pre-defined keywords. From 15,839 unique records, three reviewers manually identified 39 relevant papers based on pre-specified inclusion and exclusion criteria. In the ChatGPT experiment, over 10% of records were randomly chosen as the experimental dataset, including the 39 manually identified manuscripts. These unique records (n=1,680) underwent screening via ChatGPT-4 using the same prespecified criteria. Four strategies were employed including standard prompting, i.e., input-output (IO), chain of thought with zero-shot learning (0-CoT), CoT with few-shot learning (FS-CoT), and Majority Voting (which integrates all three promoting strategies). Performance of the models were assessed using recall, F-score, and precision measures.

Results

Recall scores (% of true abstracts successfully identified and retrieved by the model from all input data/records) for different ChatGPT configurations were 0.82 (IO), 0.97 (0-CoT), and both the FS-CoT and the Majority Voting prompts achieved a recall score of 1.0. F-scores were 0.34 (IO), 0.29 (0-CoT), 0.39 (FS-CoT), and 0.46 (majority voting). Precision measures were 0.22(IO), 0.17(0-CoT), 0.24(FS-CoT), and 0.30 (Majority Voting). Computational time varied with 2.32, 4.55, 6.44, and 13.30 hours for IO, 0-CoT, FS-CoT, and majority voting,respectively. Processing costs for the 1,680 unique records were approximately $63, $73, $186, and $325, respectively.

Conclusion

LLMs, like ChatGPT, are viable for systematic reviews, efficiently identifying studies meeting pre-specified criteria. Greater efficacy was observed when a more sophisticated prompt design was employed, integrating IO, 0-CoT and FS-CoT prompt techniques (i.e., majority voting). LLMs can expedite the study selection process in systematic reviews compared to manual methods, with minimal cost implications.
Genomic recombination of rapidly evolving mpox Ib strains compounds the challenges of the 2024 outbreak
Authors: Yeh Ting-Yu , Feehley Patrick J. , Feeley Michael C. , Chen Chieh-Fan , Tsai Tung-Yuan , Cheng Hsiang-Lan , Contreras Gregory P.
Published: September 2024

The World Health Organization recently declared the 2024 mpox virus (MPXV Ib) outbreak a public health emergency of international concern. We report that in 2023-2024, MPXV clade Ib genomes are diverging at a faster rate than clade IIb (2022), primarily due to an unusually high incidence of recombination. Phylogenetic analysis revealed that Ib strains have diverged into four lineages, and they have evolved into 14 subgroups based on nine tandem repeat (TR) polymorphisms. These findings confirms that TRs in MPXV Ib are mutating at a significantly higher frequency compared to the 2022 outbreak (clade IIb, 11 subgroups). Linkage disequilibrium analysis also identified 10 recombination clusters among all 4 lineages, with recombination incidence in Ib being twice as high as in IIb. This suggests that a higher rate of superinfection is contributing to ongoing recombination among populations infected with clade Ib. Prompt action is necessary to prevent the emergence of more lethal mpox strains.
FUS controls muscle differentiation and structure through LLPS mediated recruitment of MEF2 and ETV5
Authors: Picchiarelli Gina , Wienand Anne , Megat Salim , Aly Amr , Been Marije , Mishra Nibha , Hutten Saskia , Sternburg Erin , Cauchy Pierre , Dieterle Stéphane , Catinozzi Marica , Demais Valérie , Tzeplaeff Laura , Huebers Annemarie , Zeuschner Dagmar , Rosenbohm Angela , Ludolph Albert C. , Boutillier Anne-Laurence , Boeckers Tobias , Dormann Dorothee , Demestre Maria , Sellier Chantal , Lagier-Tourenne Clotilde , Storkebaum Erik , Dupuis Luc
Published: September 2024

FUS is an RNA binding protein mutated in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive muscle weakness. We show that ALS-associatedFUSmutations lead to ultrastructural defects in muscle ofFUS-ALS patients, with disruption of sarcomeres and mitochondria. Studies in mouse andDrosophilamodels demonstrate an evolutionary-conserved cell autonomous function of FUS in muscle development. Mechanistically, FUS is required for transcription of MEF2 dependent genes, binds to the promoter of genes bound by ETS transcription factors in particular ETV5 and co-activates transcription of MEF2 dependent genes with ETV5. FUS phase separates with ETV5 and MEF2A, and MEF2A binding to FUS is potentiated by ETV5. Last,Etv5haploinsufficiency exacerbates muscle weakness in a mouse model ofFUS-ALS. These findings establish FUS as an essential protein for skeletal muscle structure through its phase separation-dependent recruitment of ETV5 and MEF2, defining a novel pathway compromised inFUS-ALS.
Optogenetic stimulation of dorsal striatum bidirectionally controls seizures
Authors: Hyder Safwan K. , Lazarini-Lopes Willian , Toib Jonathan , Williams Gabrielle , Sukharev Alex , Forcelli Patrick A.
Published: September 2024

Engagement of the striatum (caudate/putamen) and other basal ganglia nuclei during seizures was first observed over 75 years ago. Basal ganglia output nuclei, and the substantia nigra pars reticulata, in particular, have well-established anti-seizure effects across a large array of experimental models. However, striatal control of seizures is understudied. To address this gap, we used optogenetic approaches to activate and inactivate neurons in the dorsal striatum of Sprague-Dawley rats submitted to the gamma-butyrolactone (GBL) model of absence epilepsy, amygdala kindling model of temporal lobe epilepsy, and pilocarpine-induced Status Epilepticus (SE). All tests were performed on a within-subject basis. Animals were tested in two different light frequencies (5 Hz and 100 Hz). Open-loop (continuous light delivery) optogenetic activation of the dorsal striatal neurons robustly suppressed seizures in all models. On the other hand, optogenetic silencing of the dorsal striatal neurons increased absence seizure expression and facilitated SE onset but had no effect on kindled limbic seizures. In the GBL model, we also verified if the closed- loop strategy (light delivery in response to seizure detection) would be enough to induce antiseizure effects. On-demand light delivery in ChR2-expressing animals reduced SWD duration, while the same approach in ArchT-expressing animals increased SWD duration. These results demonstrated previously unrecognized anti-absence effects associated with striatal continuous and on-demand neuromodulation. Together, these findings document a robust, bidirectional role of the dorsal striatum in the control of seizure generation and propagation in a variety of seizure models, including focal seizure onset and generalized seizures.