bluuebunny/crossref_metadata_2025 huggingface dataset:
Readiness of health facilities to manage individuals infected with COVID-19, Uganda, June 2021
Authors: Mwine Patience , Atuhaire Immaculate , Ahirirwe Sherry R. , Nansikombi Hilda T. , Senyange Shaban , Elayeete Sarah , Masanja Veronicah , Asio Alice , Komakech Allan , Nampeera Rose , Nsubuga Edirisa J. , Nakamya Petranilla , Kwiringira Andrew , Migamba Stella M. , Kwesiga Benon , Kadobera Daniel , Bulage Lillian , Okello Paul E. , Nabatanzi Sandra , Monje Fred , Kyamwine Irene B. , Ario Alex R. , Harris Julie R.
Published: May 2023

Background

The COVID-19 pandemic overwhelmed the capacity of health facilities globally, emphasizing the need for readiness to respond to rapid increases in cases. The first wave of COVID-19 in Uganda peaked in late 2020 and demonstrated challenges with facility readiness to manage cases. The second wave began in May 2021. In June 2021, we assessed the readiness of health facilities in Uganda to manage the second wave of COVID-19.

Methods

Referral hospitals managed severe COVID-19 patients, while lower-level health facilities screened, isolated, and managed mild cases. We assessed 17 of 20 referral hospitals in Uganda and 71 of 3,107 lower-level health facilities, selected using multistage sampling. We interviewed health facility heads in person about case management, coordination and communication and reporting, and preparation for the surge of COVID-19 during first and the start of the second waves of COVID-19, inspected COVID-19 treatment units (CTUs) and other service delivery points. We used an observational checklist to evaluate capacity in infection prevention, medicines, personal protective equipment (PPE), and CTU surge capacity. We used the “ReadyScore” criteria to classify readiness levels as > 80% (‘ready’), 40–80% (‘work to do’), and < 40% (‘not ready’) and tailored the assessments to the health facility level. Scores for the lower-level health facilities were weighted to approximate representativeness for their health facility type in Uganda.

Results

The median (interquartile range (IQR)) readiness scores were: 39% (IQR: 30, 51%) for all health facilities, 63% (IQR: 56, 75%) for referral hospitals, and 32% (IQR: 24, 37%) for lower-level facilities. Of 17 referral facilities, two (12%) were ‘ready’ and 15 (88%) were in the “work to do” category. Fourteen (82%) had an inadequate supply of medicines, 12 (71%) lacked adequate supply of oxygen, and 11 (65%) lacked space to expand their CTU. Fifty-five (77%) lower-level health facilities were “not ready,” and 16 (23%) were in the “work to do” category. Seventy (99%) lower-level health facilities lacked medicines, 65 (92%) lacked PPE, and 53 (73%) lacked an emergency plan for COVID-19.

Conclusion

Few health facilities were ready to manage the second wave of COVID-19 in Uganda during June 2021. Significant gaps existed for essential medicines, PPE, oxygen, and space to expand CTUs. The Uganda Ministry of Health utilized our findings to set up additional COVID-19 wards in hospitals and deliver medicines and PPE to referral hospitals. Adequate readiness for future waves of COVID-19 requires additional support and action in Uganda.
Evaluation of the implementation progress through key performance indicators in a new multimorbidity patient-centered care model in Chile
Authors: Varela Teresita , Zamorano Paula , Muñoz Paulina , Rain Carolina , Irazoqui Esteban , Sapag Jaime C. , Tellez Alvaro
Published: May 2023

Background

Complex health interventions involve deep organizational, structural, and cultural changes that challenge health teams and decision-makers. The explosion of chronic diseases has made the multimorbidity approach a global priority. The Centro de Innovación en Salud ANCORA UC implemented a Multimorbidity Patient-Centered Care Model in the Chilean public health system.

Objective

This study aims to evaluate the progress of the implementation of the Multimorbidity Patient-Centered Care Model in seven primary care centers through key performance indicators.

Methods

a set of indicators was designed to evaluate change management, operations, installation of new roles, and services and activities of the intervention strategy of the model. Key performance indicators were identified to monitor the implementation progress on minimal components for the model’s sustainability. Each item was assigned against an expected minimum score of 67% of progress from the overall score. They were monitored twice in seven primary health centers in 2019 and 2020, which intervened 22,642 patients with the intervention.

Results

The results showed that six of the seven primary care centers reached the minimum implementation threshold. The main advances were in operational conditions, and those with minor progress in implementation were the clinical services. Population size, organization, coordination of the health care teams, additional training, and decision-makers support were key factors that determined the degree of progress in a complex intervention.

Conclusion

It was possible to measure the progression of the implementation of a complex intervention through key performance indicators delivering relevant information for decision-makers that pursue a successful and faithful implementation. This study provides a valuable tool for the national scale-up of a similar model started in Chile by the Ministry of Health and other countries.
Association between chronic pain and risk of incident dementia: findings from a prospective cohort
Authors: Tian Jing , Jones Graeme , Lin Xin , Zhou Yuan , King Anna , Vickers James , Pan Feng
Published: May 2023

Background

Chronic musculoskeletal pain has been linked to dementia; however, chronic pain typically occurs in multiple sites; therefore, this study was to investigate whether greater number of chronic pain sites is associated with a higher risk of dementia and its subtypes.

Methods

Participants (N = 356,383) in the UK Biobank who were dementia-free at baseline were included. Pain in the hip, knee, back, and neck/shoulder or ‘all over the body’ and its duration were assessed. Participants were categorised into six groups: no chronic pain; chronic pain in 1, 2, 3, and 4 sites, and ‘all over the body’. All-cause dementia and its subtypes were ascertained using hospital inpatient and death registry records. Cox regression was used to investigate the associations between the number of chronic pain sites and the incidence of all-cause dementia and its subtypes.

Results

Over a median follow-up of 13 years, 4959 participants developed dementia. After adjustment for sociodemographic, lifestyle, comorbidities, pain medications, psychological problems, and sleep factors, greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia (hazard ratio [HR] = 1.08 per 1 site increase, 95% CI 1.05–1.11) and Alzheimer’s disease (AD) (HR = 1.09 per 1-site increase, 95% CI 1.04–1.13) in a dose–response manner but not vascular and frontotemporal dementia. No significant association was found between the number of chronic pain sites and the risk of incident all-cause dementia among a subsample that underwent a fluid intelligence test.

Conclusions

Greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia and AD, suggesting that chronic pain in multiple sites may contribute to individuals’ dementia risk and is an underestimated risk factor for dementia.
Investigating the relationship between depression and breast cancer: observational and genetic analyses
Authors: Wu Xueyao , Zhang Wenqiang , Zhao Xunying , Zhang Li , Xu Minghan , Hao Yu , Xiao Jinyu , Zhang Ben , Li Jiayuan , Kraft Peter , Smoller Jordan W. , Jiang Xia
Published: May 2023

Background

Both depression and breast cancer (BC) contribute to a substantial global burden of morbidity and mortality among women, and previous studies have observed a potential depression-BC link. We aimed to comprehensively characterize the phenotypic and genetic relationships between depression and BC.

Methods

We first evaluated phenotypic association using longitudinal follow-up data from the UK Biobank (N = 250,294). We then investigated genetic relationships leveraging summary statistics from the hitherto largest genome-wide association study of European individuals conducted for depression (N = 500,199), BC (N = 247,173), and its subtypes based on the status of estrogen receptor (ER + : N = 175,475; ER − : N = 127,442).

Results

Observational analysis suggested an increased hazard of BC in depression patients (HR = 1.10, 95%CIs = 0.95–1.26). A positive genetic correlation between depression and overall BC was observed ($${r}_{g}$$

r
g

= 0.08, P = 3.00 × 10–4), consistent across ER + ($${r}_{g}$$

r
g

= 0.06, P = 6.30 × 10–3) and ER − subtypes ($${r}_{g}$$

r
g

= 0.08, P = 7.20 × 10–3). Several specific genomic regions showed evidence of local genetic correlation, including one locus at 9q31.2, and four loci at, or close, to 6p22.1. Cross-trait meta-analysis identified 17 pleiotropic loci shared between depression and BC. TWAS analysis revealed five shared genes. Bi-directional Mendelian randomization suggested risk of depression was causally associated with risk of overall BC (OR = 1.12, 95%Cis = 1.04–1.19), but risk of BC was not causally associated with risk of depression.

Conclusions

Our work demonstrates a shared genetic basis, pleiotropic loci, and a putative causal relationship between depression and BC, highlighting a biological link underlying the observed phenotypic relationship; these findings may provide important implications for future studies aimed reducing BC risk.
Lower heart rate variability, an index of worse autonomic function, is associated with worse beta cell response to a glycemic load in vivo—The Maastricht Study
Authors: Rinaldi Elisabetta , van der Heide Frank CT , Bonora Enzo , Trombetta Maddalena , Zusi Chiara , Kroon Abraham A , Schram Miranda T , van der Kallen Carla JH , Wesselius Anke , Bonadonna Riccardo , Mari Andrea , Schalkwijk Casper G , van Greevenbroek Marleen MJ , Stehouwer Coen DA
Published: May 2023

Objective

We investigated, using population-based data, whether worse autonomic function, estimated from lower 24-hour heart rate variability (HRV), was associated with beta cell function, assessed from beta cell response during an oral glucose tolerance test (OGTT).

Research design and methods

We used cross-sectional data from The Maastricht Study, a population-based cohort study (N = 2,007; age, mean ± SD:60 ± 8 years; 52% men; and 24% with type 2 diabetes). We used linear regression analyses with adjustment for potential confounders (demographic, cardiovascular, and lifestyle factors) to study the associations of time- and frequency-domain HRV (composite scores) with overall beta cell response (estimated from a composite score calculated from: C-peptidogenic index, overall insulin secretion, beta cell glucose sensitivity, beta cell potentiation factor, and beta cell rate sensitivity). In addition, we tested for interaction by sex and glucose metabolism status.

Results

After full adjustment, lower time- and frequency-domain HRV was significantly associated with lower overall beta cell response composite score (standardized beta, -0.055 [-0.098; -0.011] and − 0.051 [-0.095; -0.007], respectively). These associations were not modified by sex and there was no consistent pattern of interaction by glucose metabolism status.

Conclusion

The present etiological study found that worse autonomic function, estimated from lower HRV, was associated with worse beta cell function, estimated from a composite score in a population-based sample which covered the entire spectrum of glucose metabolism. Hence, autonomic dysfunction may contribute to beta cell dysfunction and, ultimately, to the alteration of glucose metabolism status from normal glucose metabolism to prediabetes and type 2 diabetes.
Promoting AMPK/SR-A1-mediated clearance of HMGB1 attenuates chemotherapy-induced peripheral neuropathy
Authors: Yang Xing , Jia Rumeng , Hu Fan , Fan Wen , Lin Tongtong , Zhang Xiaotao , Xu Chenjie , Ruan Shirong , Jiang Chunyi , Li Yan , Pan Cailong , Yang Yang , Hu Liang , Chen Qi , Liu Wen-Tao
Published: May 2023

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of chemotherapy with poorly understood mechanisms and few treatments. High-mobility group box 1 (HMGB1)-induced neuroinflammation is the main cause of CIPN. Here, we aimed to illustrate the role of the macrophage scavenger receptor A1 (SR-A1) in HMGB1 clearance and CIPN resolution.

Methods

Oxaliplatin (L-OHP) was used to establish a CIPN model. Recombinant HMGB1 (rHMGB1) (his tag) was used to evaluate the phagocytosis of HMGB1 by macrophages.

Results

In the clinic, HMGB1 expression and MMP-9 activity were increased in the plasma of patients with CIPN. Plasma HMGB1 expression was positively correlated with the cumulative dose of L-OHP and the visual analog scale. In vitro, engulfment and degradation of rHMGB1 increased and inflammatory factor expression decreased after AMP-activated protein kinase (AMPK) activation. Neutralizing antibodies, inhibitors, or knockout of SR-A1 abolished the effects of AMPK activation on rHMGB1 engulfment. In vivo, AMPK activation increased SR-A1 expression in the dorsal root ganglion, decreased plasma HMGB1 expression and MMP-9 activity, and attenuated CIPN, which was abolished by AMPK inhibition or SR-A1 knockout in the CIPN mice model.

Conclusion

Activation of the AMPK/SR-A1 axis alleviated CIPN by increasing macrophage-mediated HMGB1 engulfment and degradation. Therefore, promoting HMGB1 clearance may be a potential treatment strategy for CIPN.
Awareness, use and understanding of nutrition labels among children and youth from six countries: findings from the 2019 – 2020 International Food Policy Study
Authors: Hammond David , Acton Rachel B. , Rynard Vicki L. , White Christine M. , Vanderlee Lana , Bhawra Jasmin , Reyes Marcela , Jáuregui Alejandra , Adams Jean , Roberto Christina A. , Sacks Gary , Thrasher James F.
Published: May 2023

Background

Nutrition facts tables (NFTs) on pre-packaged foods are widely used but poorly understood by consumers. Several countries have implemented front-of-package labels (FOPLs) that provide simpler, easier to use nutrition information. In October 2020, Mexico revised its FOPL regulations to replace industry-based Guideline Daily Amount (GDA) FOPLs with ‘Warning’ FOPLs, which display stop signs on foods high in nutrients of concern, such as sugar and sodium. This study examined self-reported awareness, use, and understanding of NFTs and FOPLs among young people in six countries with different FOPLs, with an additional focus on changes before and after implementation of Mexico’s FOPL warning policy.

Methods

A ‘natural experiment’ was conducted using ‘pre-post’ national surveys in Mexico and five separate comparison countries: countries with no FOPL policy (Canada and the US), countries with voluntary FOPL policies (Traffic Lights in the UK and Health Star Ratings in Australia), and one country (Chile) with mandatory FOPL ‘warnings' (like Mexico). Population-based surveys were conducted with 10 to 17-year-olds in 2019 (n = 10,823) and in 2020 (n = 11,713). Logistic regressions examined within- and between-countries changes in self-reported awareness, use, and understanding of NFTs and FOPLs.

Results

Across countries, half to three quarters of respondents reported seeing NFTs ‘often’ or ‘all the time’, approximately one quarter reported using NFTs when deciding what to eat or buy, and one third reported NFTs were ‘easy to understand’, with few changes between 2019 and 2020. In 2020, awareness, use and self-reported understanding of the Warning FOPLs in Mexico were higher than for NFTs in all countries, and compared with GDA FOPLs in Mexico (p < .001). Mandated Warning FOPLs in Mexico and Chile had substantially higher levels of awareness, use, and understanding than the voluntary Traffic Lights in the UK and Health Star Ratings in Australia (p < .001 for all).

Conclusions

Mandated easy-to-understand FOPLs are associated with substantially greater levels of self-reported awareness, use and understanding at the population-level compared to NFT and GDA-based labeling systems.
Can vibrotactile stimulation and tDCS help inefficient BCI users?
Authors: Won Kyungho , Kim Heegyu , Gwon Daeun , Ahn Minkyu , Nam Chang S. , Jun Sung Chan
Published: May 2023

Brain-computer interface (BCI) has helped people by allowing them to control a computer or machine through brain activity without actual body movement. Despite this advantage, BCI cannot be used widely because some people cannot achieve controllable performance. To solve this problem, researchers have proposed stimulation methods to modulate relevant brain activity to improve BCI performance. However, multiple studies have reported mixed results following stimulation, and the comparative study of different stimulation modalities has been overlooked. Accordingly, this study was designed to compare vibrotactile stimulation and transcranial direct current stimulation’s (tDCS) effects on brain activity modulation and motor imagery BCI performance among inefficient BCI users. We recruited 44 subjects and divided them into sham, vibrotactile stimulation, and tDCS groups, and low performers were selected from each stimulation group. We found that the latter’s BCI performance in the vibrotactile stimulation group increased significantly by 9.13% (p < 0.01), and while the tDCS group subjects’ performance increased by 5.13%, it was not significant. In contrast, sham group subjects showed no increased performance. In addition to BCI performance, pre-stimulus alpha band power and the phase locking values (PLVs) averaged over sensory motor areas showed significant increases in low performers following stimulation in the vibrotactile stimulation and tDCS groups, while sham stimulation group subjects and high performers showed no significant stimulation effects across all groups. Our findings suggest that stimulation effects may differ depending upon BCI efficiency, and inefficient BCI users have greater plasticity than efficient BCI users.
Pathogenicity and immunogenicity of gI/gE/TK-gene-deleted Felid herpesvirus 1 variants in cats
Authors: Tang Aoxing , Zhu Meng , Zhu Jie , Zhang Da , Zhu Shiqiang , Wang Xiao , Meng Chunchun , Li Chuangfeng , Liu Guangqing
Published: May 2023

Background

Felid herpesvirus 1 (FHV-1) is a major pathogenic agent of upper respiratory tract infections and eye damage in felines worldwide. Current FHV-1 vaccines offer limited protection of short duration, and therefore, do not reduce the development of clinical signs or the latency of FHV-1.

Methods

To address these shortcomings, we constructed FHV ∆gIgE-eGFP, FHV ∆TK mCherry, and FHV ∆gIgE/TK eGFP-mCherry deletion mutants (ΔgI/gE, ΔTK, and ΔgIgE/TK, respectively) using the clustered regularly interspaced palindromic repeats (CRISPR)/CRISP-associated protein 9 (Cas9) system (CRISPR/Cas9), which showed safety and immunogenicity in vitro. We evaluated the safety and efficacy of the deletion mutants administered with intranasal (IN) and IN + subcutaneous (SC) vaccination protocols. Cats in the vaccination group were vaccinated twice at a 4-week interval, and all cats were challenged with infection 3 weeks after the last vaccination. The cats were assessed for clinical signs, nasal shedding, and virus-neutralizing antibodies (VN), and with postmortem histological testing.

Results

Vaccination with the gI/gE-deleted and gI/gE/TK-deleted mutants was safe and resulted in significantly lower clinical disease scores, fewer pathological changes, and less nasal virus shedding after infection. All three mutants induced virus-neutralizing antibodies after immunization.

Conclusions

In conclusion, this study demonstrates the advantages of FHV-1 deletion mutants in preventing FHV-1 infection in cats.
Indigenous communities’ perceptions reveal threats and management options of wild edible plants in semiarid lands of northwestern Kenya
Authors: Oluoch Wyclife Agumba , Whitney Cory , Termote Céline , Borgemeister Christian , Schmitt Christine B.
Published: May 2023

Background

Understanding how local communities perceive threats and management options of wild edible plants (WEPs) is essential in developing their conservation strategies and action plans. Due to their multiple use values, including nutrition, medicinal, construction, and cultural as well as biotic and abiotic pressures, WEPs are exposed to overexploitation, especially within arid and semiarid lands, and hence the need to manage and conserve them. We demonstrate how an understanding of indigenous communities’ perceptions could be achieved through an integrated participatory approach involving focus group discussions (FGDs) and field plot surveys.

Methods

We conducted three FGDs between October 2020 and April 2021 within three community units in northwestern Kenya with different socioeconomic and environmental characteristics. We subsequently surveyed 240 field plots of size 1 ha each to assess threats facing WEPs within a 5 km buffer radius in every study community. We compared ranks of threats and management options across community units.

Results

Rankings of threats and management options differed across the three study communities. We obtained strong positive linear relationships between field and FGD rankings of threats facing WEPs. Climate change, overstocking, overharvesting, and invasive species were the highest-ranked threats. Mitigation of climate change, local knowledge preservation, selection, propagation, processing, and marketing of WEPs ranked high among possible management options irrespective of the socioeconomic and environmental characteristics of the community unit.

Conclusions

Our approach emphasizes the relevance of leveraging indigenous communities’ perceptions and conducting field plot surveys to assess threats and management options for WEPs. Evaluating the effectiveness and cost–benefit implications of implementing the highly ranked management options could help determine potentially suitable habitats of the WEPs for conservation and management purposes, especially for priority WEPs.
Integrative network fusion-based multi-omics study for biomarker identification and patient classification of rheumatoid arthritis
Authors: Ding Zihe , Chen Wenjia , Wu Hao , Li Weijie , Mao Xia , Su Weiwei , Zhang Yanqiong , Lin Na
Published: May 2023

Background

Cold-dampness Syndrome (RA-Cold) and Hot-dampness Syndrome (RA-Hot) are two distinct groups of rheumatoid arthritis (RA) patients with different clinical symptoms based on traditional Chinese medicine (TCM) theories and clinical empirical knowledge. However, the biological basis of the two syndromes has not been fully elucidated, which may restrict the development of personalized medicine and drug discovery for RA diagnosis and therapy.

Methods

An integrative strategy combining clinical transcriptomics, phenomics, and metabolomics data based on clinical cohorts and adjuvant-induced arthritis rat models was performed to identify novel candidate biomarkers and to investigate the biological basis of RA-Cold and RA-Hot.

Results

The main clinical symptoms of RA-Cold patients are joint swelling, pain, and contracture, which may be associated with the dysregulation of T cell-mediated immunity, osteoblast differentiation, and subsequent disorders of steroid biosynthesis and phenylalanine metabolism. In contrast, the main clinical symptoms of RA-Hot patients are fever, irritability, and vertigo, which may be associated with various signals regulating angiogenesis, adrenocorticotropic hormone release, and NLRP3 inflammasome activation, leading to disorders of steroid biosynthesis, nicotinamide, and sphingolipid metabolism. IL17F, 5-HT, and IL4I1 were identified as candidate biomarkers of RA-Cold, while S1P and GLNS were identified as candidate biomarkers of RA-Hot.

Conclusions

The current study presents the most comprehensive metabonomic and transcriptomic profiling of serum, urine, synovial fluid, and synovial tissue samples obtained from RA-Cold and RA-Hot patients and experimental animal models to date. Through the integration of multi-omics data and clinical independent validation, a list of novel candidate biomarkers of RA-Cold and RA-Hot syndromes were identified, that may be useful in improving RA diagnosis and therapy.
Pediatric joint hypermobility: a diagnostic framework and narrative review
Authors: Tofts Louise Jane , Simmonds Jane , Schwartz Sarah B. , Richheimer Roberto M. , O’Connor Constance , Elias Ellen , Engelbert Raoul , Cleary Katie , Tinkle Brad T. , Kline Antonie D. , Hakim Alan J. , van Rossum Marion A. J. , Pacey Verity
Published: May 2023

Background

Hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are debilitating conditions. Diagnosis is currently clinical in the absence of biomarkers, and criteria developed for adults are difficult to use in children and biologically immature adolescents. Generalized joint hypermobility (GJH) is a prerequisite for hEDS and generalized HSD. Current literature identifies a large proportion of children as hypermobile using a Beighton score ≥ 4 or 5/9, the cut off for GJH in adults. Other phenotypic features from the 2017 hEDS criteria can arise over time. Finally, many comorbidities described in hEDS/HSD are also seen in the general pediatric and adolescent population. Therefore, pediatric specific criteria are needed. The Paediatric Working Group of the International Consortium on EDS and HSD has developed a pediatric diagnostic framework presented here. The work was informed by a review of the published evidence.

Observations

The framework has 4 components, GJH, skin and tissue abnormalities, musculoskeletal complications, and core comorbidities. A Beighton score of ≥ 6/9 best identifies children with GJH at 2 standard deviations above average, based on published general population data. Skin and soft tissue changes include soft skin, stretchy skin, atrophic scars, stretch marks, piezogenic papules, and recurrent hernias. Two symptomatic groups were agreed: musculoskeletal and systemic. Emerging comorbid relationships are discussed. The framework generates 8 subgroups, 4 pediatric GJH, and 4 pediatric generalized hypermobility spectrum disorders. hEDS is reserved for biologically mature adolescents who meet the 2017 criteria, which also covers even rarer types of Ehlers–Danlos syndrome at any age.

Conclusions

This framework allows hypermobile children to be categorized into a group describing their phenotypic and symptomatic presentation. It clarifies the recommendation that comorbidities should be defined using their current internationally accepted frameworks. This provides a foundation for improving clinical care and research quality in this population.
Targeting homologous recombination deficiency in uterine leiomyosarcoma
Authors: Dall Genevieve , Vandenberg Cassandra J. , Nesic Ksenija , Ratnayake Gayanie , Zhu Wenying , Vissers Joseph H. A. , Bedő Justin , Penington Jocelyn , Wakefield Matthew J. , Kee Damien , Carmagnac Amandine , Lim Ratana , Shield-Artin Kristy , Milesi Briony , Lobley Amanda , Kyran Elizabeth L. , O’Grady Emily , Tram Joshua , Zhou Warren , Nugawela Devindee , Stewart Kym Pham , Caldwell Reece , Papadopoulos Lia , Ng Ashley P. , Dobrovic Alexander , Fox Stephen B. , McNally Orla , Power Jeremy D. , Meniawy Tarek , Tan Teng Han , Collins Ian M. , Klein Oliver , Barnett Stephen , Olesen Inger , Hamilton Anne , Hofmann Oliver , Grimmond Sean , Papenfuss Anthony T. , Scott Clare L. , Barker Holly E.
Published: May 2023

Background

Uterine leiomyosarcoma (uLMS) is a rare and aggressive gynaecological malignancy, with individuals with advanced uLMS having a five-year survival of < 10%. Mutations in the homologous recombination (HR) DNA repair pathway have been observed in ~ 10% of uLMS cases, with reports of some individuals benefiting from poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy, which targets this DNA repair defect. In this report, we screened individuals with uLMS, accrued nationally, for mutations in the HR repair pathway and explored new approaches to therapeutic targeting.

Methods

A cohort of 58 individuals with uLMS were screened for HR Deficiency (HRD) using whole genome sequencing (WGS), whole exome sequencing (WES) or NGS panel testing. Individuals identified to have HRD uLMS were offered PARPi therapy and clinical outcome details collected. Patient-derived xenografts (PDX) were generated for therapeutic targeting.

Results

All 13 uLMS samples analysed by WGS had a dominant COSMIC mutational signature 3; 11 of these had high genome-wide loss of heterozygosity (LOH) (> 0.2) but only two samples had a CHORD score > 50%, one of which had a homozygous pathogenic alteration in an HR gene (deletion in BRCA2). A further three samples harboured homozygous HRD alterations (all deletions in BRCA2), detected by WES or panel sequencing, with 5/58 (9%) individuals having HRD uLMS. All five individuals gained access to PARPi therapy. Two of three individuals with mature clinical follow up achieved a complete response or durable partial response (PR) with the subsequent addition of platinum to PARPi upon minor progression during initial PR on PARPi. Corresponding PDX responses were most rapid, complete and sustained with the PARP1-specific PARPi, AZD5305, compared with either olaparib alone or olaparib plus cisplatin, even in a paired sample of a BRCA2-deleted PDX, derived following PARPi therapy in the patient, which had developed PARPi-resistance mutations in PRKDC, encoding DNA-PKcs.

Conclusions

Our work demonstrates the value of identifying HRD for therapeutic targeting by PARPi and platinum in individuals with the aggressive rare malignancy, uLMS and suggests that individuals with HRD uLMS should be included in trials of PARP1-specific PARPi.
Some weak type inequalities and almost everywhere convergence of Vilenkin–Nörlund means
Authors: Baramidze Davit , Nadirashvili Nato , Persson Lars-Erik , Tephnadze George
Published: May 2023

We prove and discuss some new weak type $(1,1 ) $
(
1
,
1
)
inequalities of maximal operators of Vilenkin–Nörlund means generated by monotone coefficients. Moreover, we use these results to prove a.e. convergence of such Vilenkin–Nörlund means. As applications, both some well-known and new inequalities are pointed out.
The Lax pair structure for the spin Benjamin–Ono equation
Authors: Gérard Patrick
Published: May 2023

We prove that the recently introduced spin Benjamin–Ono equation admits a Lax pair and deduce a family of conservation laws that allow proving global wellposedness in all Sobolev spaces $H^{k}$

H
k

for every integer $k\geq 2$
k
≥
2
. We also infer an additional family of matrix-valued conservation laws of which the previous family is just the traces.
Lesser omental hernia through a defect in the posterior layer of the lesser omentum
Authors: Shibuya Hirotaka , Sato Keita , Yamauchi Yosuke , Tamura Yoshihisa , Takahashi Koji , Asari Yasushi
Published: May 2023

Background

In previously reported cases of lesser omental hernia, a rare clinical presentation, the herniated intestinal tract was passing through both peritoneal layers of the lesser omentum to herniate into the peritoneal cavity or bursa omentalis. Here we present a very rare case of lesser omentum hernia, where the transverse colon entered through only the posterior layer of the lesser omentum to form a hernia between the anterior and posterior layers.

Case presentation

A 43-year-old man was admitted to the emergency department with acute abdominal pain. Plain abdominal computed tomography (CT) revealed a change in the caliber of the transverse colon between the stomach and pancreas, forming a closed loop on the cephaloventral side of the stomach. On contrast-enhanced CT images, vessels were observed in the contrast-enhanced lesser omentum surrounding the herniated intestine. The patient was diagnosed with a lesser omental hernia and underwent laparoscopic surgery. Intraoperatively, the transverse colon was covered by the anterior layer of the lesser omentum, and a defect was found in the posterior layer of the lesser omentum on the dorsal side of the stomach. A 2-cm incision was made in the posterior layer of the lesser omentum to widen the small defect. The herniated intestinal section was removed from the hernia sac, and the transverse colon was retained unresected. The postoperative course was uneventful.

Conclusions

As illustrated in this first case of a lesser omental hernia forming between the anterior and posterior layers, characteristic CT findings may play an active role in the diagnosis of this rare presentation.
Application of molecular dynamics simulation in self-assembled cancer nanomedicine
Authors: Xu Xueli , Liu Ao , Liu Shuangqing , Ma Yanling , Zhang Xinyu , Zhang Meng , Zhao Jinhua , Sun Shuo , Sun Xiao
Published: May 2023

Self-assembled nanomedicine holds great potential in cancer theragnostic. The structures and dynamics of nanomedicine can be affected by a variety of non-covalent interactions, so it is essential to ensure the self-assembly process at atomic level. Molecular dynamics (MD) simulation is a key technology to link microcosm and macroscale. Along with the rapid development of computational power and simulation methods, scientists could simulate the specific process of intermolecular interactions. Thus, some experimental observations could be explained at microscopic level and the nanomedicine synthesis process would have traces to follow. This review not only outlines the concept, basic principle, and the parameter setting of MD simulation, but also highlights the recent progress in MD simulation for self-assembled cancer nanomedicine. In addition, the physicochemical parameters of self-assembly structure and interaction between various assembled molecules under MD simulation are also discussed. Therefore, this review will help advanced and novice researchers to quickly zoom in on fundamental information and gather some thought-provoking ideas to advance this subfield of self-assembled cancer nanomedicine.
Disappearing male sterilization in India: do we care?
Authors: Salve Pradeep S. , Shekhar Chander
Published: May 2023

The disproportionate share of contraceptive use by women makes family planning services women-centric in India. The meagre and declining share of male-based contraceptive use, along with the overwhelming prevalence of female sterilization, has its underpinning in the lack of emphasis on fertility regulation with the use of temporary methods. The recent trends in the share of contraceptive choices not only contest the most touted cafeteria approach but also serves counter to the National Health Policy target of increasing vasectomy prevalence. Hence an inspection of trends in vasectomy may help in course correction needed to realise NHP targets.
Clinical surrogates of dysautonomia predict lethal outcome in COVID-19 on intensive care unit
Authors: Woo Marcel Seungsu , Mayer Christina , Fischer Marlene , Kluge Stefan , Roedl Kevin , Gerloff Christian , Czorlich Patrick , Thomalla Götz , Schulze zur Wiesch Julian , Schweingruber Nils
Published: May 2023

Background

Unpredictable vegetative deteriorations made the treatment of patients with acute COVID-19 on intensive care unit particularly challenging during the first waves of the pandemic. Clinical correlates of dysautonomia and their impact on the disease course in critically ill COVID-19 patients are unknown.

Methods

We retrospectively analyzed data collected during a single-center observational study (March 2020–November 2021) which was performed at the University Medical Center Hamburg-Eppendorf, a large tertiary medical center in Germany. All patients admitted to ICU due to acute COVID-19 disease during the study period were included (n = 361). Heart rate variability (HRV) and blood pressure variability (BPV) per day were used as clinical surrogates of dysautonomia and compared between survivors and non-survivors at different time points after admission. Intraindividual correlation of vital signs with laboratory parameters were calculated and corrected for age, sex and disease severity.

Results

Patients who deceased in ICU had a longer stay (median days ± IQR, survivors 11.0 ± 27.3, non-survivors 14.1 ± 18.7, P = 0.85), in contrast time spent under invasive ventilation was not significantly different (median hours ± IQR, survivors 322 ± 782, non-survivors 286 ± 434, P = 0.29). Reduced HRV and BPV predicted lethal outcome in patients staying on ICU longer than 10 days after adjustment for age, sex, and disease severity. Accordingly, HRV was significantly less correlated with inflammatory markers (e.g. CRP and Procalcitonin) and blood carbon dioxide in non-survivors in comparison to survivors indicating uncoupling between autonomic function and inflammation in non-survivors.

Conclusions

Our study suggests autonomic dysfunction as a contributor to mortality in critically ill COVID-19 patients during the first waves of the pandemic. Serving as a surrogate for disease progression, these findings could contribute to the clinical management of COVID-19 patients admitted to the ICU. Furthermore, the suggested measure of dysautonomia and correlation with other laboratory parameters is non-invasive, simple, and cost-effective and should be evaluated as an additional outcome parameter in septic patients treated in the ICU in the future.
Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Acute Lymphoblastic Leukemia Intercontinental-Berlin-Frankfurt-Münster 2009 Trial
Authors: Campbell Myriam , Kiss Csongor , Zimmermann Martin , Riccheri Cecilia , Kowalczyk Jerzy , Felice Maria S. , Kuzmanovic Milos , Kovacs Gabor , Kosmidis Helen , Gonzalez Alejandro , Bilic Ernest , Castillo Luis , Kolenova Alexandra , Jazbec Janez , Popa Alexander , Konstantinov Dobrin , Kappelmayer Janos , Szczepanski Tomasz , Dworzak Michael , Buldini Barbara , Gaipa Giuseppe , Marinov Neda , Rossi Jorge , Nagy Attila , Gaspar Imre , Stary Jan , Schrappe Martin
Published: May 2023

PURPOSE

The International Berlin-Frankfurt-Münster (BFM) study group conducted a study on pediatric acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) was assessed using flow cytometry (FCM), and the impact of early intensification and methotrexate (MTX) dose on survival was evaluated.

PATIENTS AND METHODS

We included 6,187 patients younger than 19 years. MRD by FCM refined the risk group definition previously used in the ALL intercontinental-BFM 2002 study on the basis of age, WBC count, unfavorable genetic aberrations, and treatment response measured morphologically. Patients at intermediate risk (IR) and high risk (HR) were randomly assigned to protocol augmented protocol I phase B (IB) versus IB regimen. MTX doses of 2 versus 5 g/m2 every 2 weeks, four times, were evaluated in precursor B-cell-ALL (pcB-ALL) IR.

RESULTS

The 5-year event-free survival (EFS ± SE) and overall survival (OS ± SE) rates were 75.2% ± 0.6% and 82.6% ± 0.5%, respectively. Their values in risk groups were standard risk (n = 624), 90.7% ± 1.4% and 94.7% ± 1.1%; IR (n = 4,111), 77.9% ± 0.7% and 85.7% ± 0.6%; and HR (n = 1,452), 60.8% ± 1.5% and 68.4% ± 1.4%, respectively. MRD by FCM was available in 82.6% of cases. The 5-year EFS rates in patients randomly assigned to protocol IB (n = 1,669) and augmented IB (n = 1,620) were 73.6% ± 1.2% and 72.8% ± 1.2%, respectively ( P = .55), while those in patients receiving MTX doses of 2 g/m2 (n = 1,056) and MTX 5 g/m2 (n = 1,027) were 78.8% ± 1.4% and 78.9% ± 1.4%, respectively ( P = .84).

CONCLUSION

The MRDs were successfully assessed using FCM. An MTX dose of 2 g/m2 was effective in preventing relapse in non-HR pcB-ALL. Augmented IB showed no advantages over the standard IB. [Media: see text]
Quantitative analysis method for extraordinary optical transmission of thin microcavity by the catastrophic theory
Authors: Zhang Lin , Wu Jiu Hui
Published: May 2023

Extraordinary optical transmission (EOT) can be regarded as a phase transition process based on the variation of the aperture of the thin microcavity by the published results. Considering that the catastrophe theory could describe quantitatively any phase transition process, a novel method is proposed to analyze the EOT transition quantitatively based on a cusp catastrophic model with dimensionless analysis. The quantitative relationship of transmitted energy spectral density is fully obtained, which is also related to the aperture radius and incident electromagnetic frequency. Furthermore, from this method, a quantum transition factor is derived strictly to describe the EOT transition process, which can be divided into wave region, wave-particle duality region and quantum region with the factor increasing from 0 to 1, and Bethe's aperture theory stating that transmission is proportional to

is only one of our special cases in the wave region. Finally, the influence of the aperture and the frequency of incident wave on the EOT transmittance is analysed, and the catastrophic model is verified by previous experiments. The novel method of transition analysis provides a new insight into the EOT.
Depression and Loneliness among the Elderly in Low- and Middle-Income Countries
Authors: Banerjee Abhijit , Duflo Esther , Grela Erin , McKelway Madeline , Schilbach Frank , Sharma Garima , Vaidyanathan Girija
Published: May 2023

We combine data from longitudinal surveys in seven low- and middle-income countries (plus the United States for comparison) to document that depressive symptoms among those aged 55 and above are prevalent in those countries and, unlike in the United States, increase sharply with age. Depressive symptoms in one survey wave are associated with a greater decline in ability to carry out basic daily activities and a higher probability of death in the next wave. Using additional data from a panel survey we conducted in Tamil Nadu with a focus on elderly living alone, we document that social isolation, poverty, and physical health challenges are strongly correlated with depression. We discuss potential policy interventions in these three domains, including some results from our randomized control trials in the Tamil Nadu sample.
What do mammals have to say about the neurobiology of acoustic communication?
Authors: Salles Angeles , Neunuebel Joshua
Published: May 2023

Auditory communication is crucial across taxa, including humans, because it enables individuals to convey information about threats, food sources, mating opportunities, and other social cues necessary for survival. Comparative approaches to auditory communication will help bridge gaps across taxa and facilitate our understanding of the neural mechanisms underlying this complex task. In this work, we briefly review the field of auditory communication processing and the classical champion animal, the songbird. In addition, we discuss other mammalian species that are advancing the field. In particular, we emphasize mice and bats, highlighting the characteristics that may inform how we think about communication processing.
State-civilization in the digital ecumene
Authors: Fedorchenko Sergey
Published: May 2023

At the beginning of the work, a brief review of the articles of the current thematic issue of the «Journal of Political Research», devoted to political aspects and problems of the worldview phenomenon, is presented. At the same time, the main goal of the article is to study the features of the construction of digital ecumene on the example of the Russian and Chinese states-civilizations. The methodological optics of this article is the principles of comparative analysis, based on the comparison of the same order, similar political phenomena, processes and phenomena. The methodological optics of this article is the principles of comparative analysis, based on the comparison of the same order, similar political phenomena, processes and phenomena. These were the state-civilizations, their civilizational features, as well as the methods of constructing their digital ecumene (state policy of foreign broadcasting; strategic regulatory documents related to the information sphere; digital diplomacy). The features of the state-civilization as a specific form of polity are compared and clarified. Also, an attempt was made to conceptualize the phenomenon of the digital ecumene – a system of news agencies, corporations, Internet resources, radio, television, leading media activity in other countries to position and protect the interests, value-civilizational, political, economic agenda of the states that created it. Such a conceptualization is based on the reception of Antiquity and correlates with the understanding of the ecumene as a sphere of influence of the state through digital technologies and communications. Such a reception also presupposes the preservation of the civilizational meaning of the ecumene. It is concluded that civilizational states have sufficient resources to maintain digital ecumene as new fields of technological and cultural strategic actions that can protect the integrity of their own civilizational cores. It has been suggested that the civilizational uncompromisingness of the West, its strategy of divide et impera, will most likely contribute to the strengthening of such a form of polity as a state-civilization. In the conditions of the existing geopolitical turbulence, the states-civilizations can focus on building a new, more just system of international relations based on the settlement of political, religious and ethnic conflicts, rather than their escalation and conservation.
Ideological aspects of the Worldview: research methodology in Political Science
Authors: Podshibyakina T.
Published: May 2023

The focus of the work is one of the types of worldview – political ideology, more specifically, methodological problems of its research. Several classical theoretical approaches of political philosophy are analyzed by the criterion of two main elements of the scientific paradigm – the origin of the phenomenon of ideology and the methodology of the study of its political aspects. The scientific problem is to find an answer to the question: how can political science, which practically does not have its own research methods, study ideology as its object. The purpose of the work is to identify the main interdisciplinary methodological approaches to the study of ideological aspects of the worldview that political science uses in its subject field. To achieve it, the following tasks are solved: analysis of ideological concepts and theories of the political and philosophical direction; identification and systematization of those that are intended for the study of the political aspect of the ideological worldview; comparative analysis of the concepts of "worldview" and "ideology" based on the criterion of common and special elements of the structure; characteristics of the features of the study of ideology in the paradigm of political science and assessment of the prospects for the development of the methodology of its research. The main method is a comparative analysis of concepts and theories. The results reflecting a certain theoretical and practical contribution of the work are presented in a generalization of the most significant approaches of political science and in recommendations on the use of a combination of methods as a theoretical and methodological construct for the study of ideology as a worldview phenomenon.
Nature Walks: A Sustainably Appreciative and Harmonious Connection with Nature
Authors: Talapatra Jayati , Verma Neena
Published: May 2023

A vibrant, bountiful planet where all species live in harmony is increasingly being recognised as a key area of focus by world leaders, corporates and communities across the globe. Along with biodiversity conservation, a green planet also addresses the twin challenges of climate change and pollution. Implementation of frameworks and guidelines to arrest biodiversity loss depends on individual commitment to change. This paper explores the impact of a nature walk in connecting people to the wonders of the planet, thereby causing more responsible behaviour towards it.