bluuebunny/crossref_metadata_2025 huggingface dataset:
End of life care for people with dementia and comorbid cancer: recent studies and research gaps
Authors: Surr Claire , Ashley Laura
Published: June 2024

Purpose of review

This narrative review examines recent research on end of life (EOL) care for people with dementia and comorbid cancer, highlighting the complexity and challenge of providing effective EOL care for this group and areas of interest for future research.

Recent findings

People with cancer and dementia and their family/supporters have more complex care and support needs at EOL that are less well met than those of older adults with cancer alone, including questionable use of aggressive EOL care interventions, poorer access to specialist palliative care teams and poor pain management. Those diagnosed with dementia at the same time as, or after their cancer diagnosis, are at greater risk of aggressive EOL care and EOL cancer treatment and care plans that are not able to meet their care needs as dementia progresses.

There is a lack of research on EOL care for people with cancer and dementia. There is little understanding of what good care for this population looks like and if and how EOL care can best meet the needs of people with cancer and dementia or their carers/supporters. More research is needed to inform improved care for this population.
Judicial Opinion 130
Authors: Arahal David R. , Bull Carolee T. , Christensen Henrik , Chuvochina Maria , Dunlap Christopher , del Carmen Montero-Calasanz Maria , Parker Charles T. , Vandamme Peter , Ventosa Antonio , Ventura Stefano , Young Peter , Göker Markus
Published: June 2024

Opinion 130 deals with a Request for an Opinion asking the Judicial Commission to clarify whether the genus name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate. The Request is approved and an answer is given. The name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate because it is a later homonym of the validly published cyanobacterial name Rhodococcus Hansgirg 1884. The Judicial Commission also clarifies that it has the means to resolve such cases by conserving a name over an earlier homonym. It is concluded that the name Rhodococcus Zopf 1891 (Approved Lists 1980) is significantly more important than the name Rhodococcus Hansgirg 1884 and therefore the former is conserved over the latter. This makes the name Rhodococcus Zopf 1891 (Approved Lists 1980) legitimate.
Colistin utilization at a tertiary hospital in South Africa: an opportunity for antimicrobial stewardship practices
Authors: Matshediso Gaalebale Prudence , Durojaiye Oyewole Christopher , Adeniyi Oladele Vincent
Published: June 2024

Introduction. Colistin (polymyxin E) has emerged as a last-resort treatment option for multidrug-resistant infections.

Hypothesis/Gap Statement. Studies on the use, safety and efficacy of colistin in South Africa are limited.

Aim. This study aims to describe the use of colistin and its clinical outcomes at a tertiary public hospital in South Africa.

Methodology. We conducted a retrospective review of adult and paediatric patients who received parenteral colistin between 2015 and 2019.

Results. A total of 69 patients (26 adults, 13 children and 30 neonates) were reviewed. Acinetobacter baumannii was the most common causative pathogen isolated (70.1 %). Colistin was predominately used to treat septicaemia (75.4 %). It was primarily administered as definitive therapy (71.0 %) and as monotherapy (56.5 %). It was used in 11.5 % of adults with infections susceptible to other antibiotics. Loading doses of intravenous colistin were administered in only 15 (57.7 %) adult patients. Neurotoxicity and nephrotoxicity occurred in 5.8 % and 43.5 % of patients, respectively. Clinical cure was achieved in 37 (53.6 %) patients. On multivariate logistic regression analysis, adults [adjusted odds ratio (aOR), 25.54; 95 % CI, 2.73–238.65; P < 0.01] and children (aOR, 8.56; 95 % CI, 1.06–69.10; P < 0.05) had higher odds of death than neonates.

Conclusion. The study identified significant stewardship opportunities to improve colistin prescription and administration. Achieving optimal patient outcomes necessitates a multidisciplinary approach and vigilant monitoring of colistin use.
Genomic sequencing and neutralizing serological profiles during acute dengue infection: A 2017 cohort study in Nepal
Authors: Prajapati Sabita , Ngono Annie Elong , Cauley Melanie Mc , Timis Julia , Shrestha Srijan , Bastola Anup , Mandal Shrawan Kumar , Yadav Sanjay Ray , Napit Rajindra , Moi Meng Ling , Yamabhai Montarop , Sessions October M , Shresta Sujan , Manandhar Krishna Das
Published: June 2024

Dengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to nearly 50% of the global population. DENV has been endemic in Nepal since 2006; however, little is known about how DENV is evolving or the prevalence of anti-DENV immunity within the Nepalese population. To begin to address these gaps, we performed a serologic and genetic study of 49 patients from across Nepal who presented at central hospitals during the 2017 dengue season with suspected DENV infection. Of the 49 subjects assessed, 21 (43%) were positive for DENV NS1 antigen; of these; 5 were also anti-DENV IgM+IgG+; 7 were DENV IgM+IgG−, 2 were IgM−IgG+, and 7 were IgM-IgG−by specific ELISAs. Seven of the 21 NS1+ sera were RNA+ by RT-PCR (six DENV2, one DENV3), suggesting that DENV2 was the dominant serotype in our cohort. Whole-genome sequencing of two DENV2 isolates showed similarity with strains circulating in Singapore in 2016, and the envelope genes were also similar to strains circulating in India in 2017. DENV-neutralizing antibodies (nAbs) were present in 31 of 47 sera tested (66%); among these, 20, 24, 26, and 12 sera contained nAbs against DENV1, 2, 3, and 4 serotypes, respectively. Serology analysis suggested that 12 (26%) and 19 (40%) of the 49 subjects were experiencing primary and secondary DENV infections, respectively. Collectively, our results provide evidence for current and/or past exposure to multiple DENV serotypes in our cohort, and the RNA analyses further indicate that DENV2 was the likely dominant serotype circulating in Nepal in 2017. These data suggest that expanded local surveillance of circulating DENV genotypes and population immunity will be important to effectively manage and mitigate future dengue outbreaks in Nepal.
Exploring Pathways to Compulsory Detention and Ways to Prevent Repeat Compulsory Detentions; Clinician Perspectives
Authors: Kular Ariana , Birken Mary , Wood Lisa , Parkinson Jordan , Bacarese-Hamilton Theresa , Blakley Louise , Hutchings-Hay Chloe , Nyikavaranda Patrick , Alam Dilshard , Ogbolu Raphael , Bendall Caroline , Tang Lai , Nickson Amy , Revell Cathryn , Mbeah-Bankas Henrietta , Mitchell Lizzie , Fraser Kathleen Lindsay , White Valerie Christina , Lobban Fiona , Lloyd-Evans Brynmor , Johnson Sonia
Published: June 2024

Background

Rates of compulsory detention in psychiatric hospitals have risen over several decades in England and some other higher income countries. This study explores clinicians’ perspectives on how service users come to be compulsorily detained in psychiatric hospitals and their suggestions for reducing these detentions in the future.

Methods

Semi-structured qualitative interviews were conducted with 23 clinicians working with individuals who have been compulsorily detained under the Mental Health Act in England. Interviews were carried out by telephone or videoconference. Data were analysed using template analysis.

Results

Three major themes were identified, with multiple sub-themes (a) service user factors that increase risk of compulsory detention, including high levels of risk, previous/underlying trauma, medication non-adherence, service user perceptions of their mental health state, disadvantage and discrimination, and lack of stability and involvement from family and social networks; (b) service-level reasons for being detained, including lack of communication and continuity of care, historical inability to obtain trust and confidence from parts of population, clinician biases and assumptions, lack of resources, lack of treatment and care variety, and systemic/institutional barriers to engagement; and (c) ways to improve services to reduce compulsory detainment, including increasing quality of care and patient/family level interventions, investing in services, offer choice regarding medication, offer alternatives to compulsory detention, and improve discharge planning.

Conclusions

Findings suggested clinicians see that at least some compulsory hospital admissions as avoidable, particularly through better resourced and more accessible services and changes in staff attitudes to address unconscious biases and promote collaborative care. Our findings provide a range of potential means to reduce detentions, which warrant development and testing in research and practice.
TYK2 as a novel therapeutic target in Alzheimer’s Disease with TDP-43 inclusions
Authors: König Laura E. , Rodriguez Steve , Hug Clemens , Daneshvari Shayda , Chung Alexander , Bradshaw Gary A. , Sahin Asli , Zhou George , Eisert Robyn J. , Piccioni Federica , Das Sudeshna , Kalocsay Marian , Sokolov Artem , Sorger Peter , Root David E. , Albers Mark W.
Published: June 2024

Neuroinflammation is a pathological feature of many neurodegenerative diseases, including Alzheimer’s disease (AD)1,2and amyotrophic lateral sclerosis (ALS)3, raising the possibility of common therapeutic targets. We previously established that cytoplasmic double-stranded RNA (cdsRNA) is spatially coincident with cytoplasmic pTDP-43 inclusions in neurons of patients with C9ORF72-mediated ALS4. CdsRNA triggers a type-I interferon (IFN-I)-based innate immune response in human neural cells, resulting in their death4. Here, we report that cdsRNA is also spatially coincident with pTDP-43 cytoplasmic inclusions in brain cells of patients with AD pathology and that type-I interferon response genes are significantly upregulated in brain regions affected by AD. We updated our machine-learning pipeline DRIAD-SP (Drug Repurposing In Alzheimer’s Disease with Systems Pharmacology) to incorporate cryptic exon (CE) detection as a proxy of pTDP-43 inclusions and demonstrated that the FDA-approved JAK inhibitors baricitinib and ruxolitinib that block interferon signaling show a protective signal only in cortical brain regions expressing multiple CEs. Furthermore, the JAK family member TYK2 was a top hit in a CRISPR screen of cdsRNA-mediated death in differentiated human neural cells. The selective TYK2 inhibitor deucravacitinib, an FDA-approved drug for psoriasis, rescued toxicity elicited by cdsRNA. Finally, we identified CCL2, CXCL10, and IL-6 as candidate predictive biomarkers for cdsRNA-related neurodegenerative diseases. Together, we find parallel neuroinflammatory mechanisms between TDP-43 associated-AD and ALS and nominate TYK2 as a possible disease-modifying target of these incurable neurodegenerative diseases.
TNBC response to paclitaxel phenocopies interferon response which reveals cell cycle-associated resistance mechanisms
Authors: Calistri Nicholas L , Liby Tiera A. , Hu Zhi , Zhang Hongmei , Dane Mark , Gross Sean M. , Heiser Laura M.
Published: June 2024

Paclitaxel is a standard of care neoadjuvant therapy for patients with triple negative breast cancer (TNBC); however, it shows limited benefit for locally advanced or metastatic disease. Here we used a coordinated experimental-computational approach to explore the influence of paclitaxel on the cellular and molecular responses of TNBC cells. We found that escalating doses of paclitaxel resulted in multinucleation, promotion of senescence, and initiation of DNA damage induced apoptosis. Single-cell RNA sequencing (scRNA-seq) of TNBC cells after paclitaxel treatment revealed upregulation of innate immune programs canonically associated with interferon response and downregulation of cell cycle progression programs. Systematic exploration of transcriptional responses to paclitaxel and cancer-associated microenvironmental factors revealed common gene programs induced by paclitaxel, IFNB, and IFNG. Transcription factor (TF) enrichment analysis identified 13 TFs that were both enriched based on activity of downstream targets and also significantly upregulated after paclitaxel treatment. Functional assessment with siRNA knockdown confirmed that the TFs FOSL1, NFE2L2 and ELF3 mediate cellular proliferation and also regulate nuclear structure. We further explored the influence of these TFs on paclitaxel-induced cell cycle behavior via live cell imaging, which revealed altered progression rates through G1, S/G2 and M phases. We found that ELF3 knockdown synergized with paclitaxel treatment to lock cells in a G1 state and prevent cell cycle progression. Analysis of publicly available breast cancer patient data showed that high ELF3 expression was associated with poor prognosis and enrichment programs associated with cell cycle progression. Together these analyses disentangle the diverse aspects of paclitaxel response and identify ELF3 upregulation as a putative biomarker of paclitaxel resistance in TNBC.
Comparative analysis of the genomic architecture of six Fusarium species
Authors: Rau Domenico , Murgia Maria Leonarda , Fois Davide , Posadinu Chiara M. , Porceddu Andrea
Published: June 2024

Comparative analyses of several plant pathogens have revealed that genome plasticity could be associated with different genomic architectures. In certain species, genomic compartments are characterised by highly conserved regions that contain mainly housekeeping genes and rearranged regions that are enriched for genes related to virulence and adaptation. The compositional and structural characteristics of genomic regions have been significantly associated with compartment membership in single species, but little information is available on the covariation of these features between species.

Here, the results of a comparative analysis of the genomic architectures of six agriculturally relevantFusariumspecies, which differ for several biological and pathogenic characteristics, are presented. These includeF. culmorum,F. fujikoroi,F. graminearum, F. oxysporum,F. solani,andF. verticillioides.

The genome sequences of these species were partitioned into adjacent windows, with the average level of gene collinearity with the other species used as an index of compartment membership. High collinearity is typical of conserved regions, while low collinearity is typical of rearranged regions. Several genic and genomic variables were found to be consistently associated with compartment definition among all theFusariumspecies that were investigated.

The compartment that was characterised by lower collinearity (i.e., high genomic rearrangements) contained more relocated genes, species-specific genes and secreted protein-encoding genes than regions with low collinearity. Furthermore, several molecular evidence indicates that low-collinearity regions are more likely to be subjected to selective pressure than high-collinearity regions. Indeed, genes residing in the former regions exhibited higher rates of sequence evolution than in the latter, as indicated by the high non-synonymous-to-synonymous substitution rates.

However, they exhibited signatures of selection to minimise the costs of transcription, as indicated by their high coding density. Our data suggests that although variable genomic compartments evolved mostly after species radiation, they share similar genomic features across related species and perhaps evolve with similar mechanisms.
The wondrous and worrying diversity of the N‐glycans ofChlorellafood supplements
Authors: Mócsai Réka , Helm Johannes , Polacsek Karin , Stadlmann Johannes , Altmann Friedrich
Published: June 2024

N-glycans have recently emerged as highly varied elements ofChlorellastrains and products. Four years and many samples later, the ever-growing N-glycan diversity shall be revisited in the light of concepts of species definition and product authenticity. N-glycans of commercial products were analyzed by matrix-assisted time-of-flight mass spectrometry (MALDI-TOF MS) supported by chromatography on porous graphitic carbon with mass spectrometric detection. While 36% of 172 products were labeledC. vulgaris, only few had matching N-glycan patterns. 5 and 20 % of the products matched withC. sorokinianastrains SAG 211-8k and SAG 211-34, respectively, which, however, carry entirely different structures. 41 % presented with four frequently occurring glyco-types while 26 % of the samples showed unique or rare N-glycan patterns. The rest presented what could be taken as aC. vulgaristype N-glycan pattern. Identical masses derive from different structures in many cases. By no means do we want to question the presumed health benefits of the products or the honest intentions of manufacturers. We rather wish to raise awareness for the fascinating but also worrying variety of microalgal N-glycans and suggest it as a means for defining product identity and taxonomic assignments.
Comprehensive Model of Cell-to-Cell Cytokinin Transport Reveals A Specific Mode of Cytokinin Riboside Influx
Authors: Nedvěd Daniel , Hudeček Martin , Klíma Petr , Lacek Jozef , Müller Karel , Hošek Petr , Šmeringai Ján , Pernisová Markéta , Motyka Václav , Plíhal Ondřej , Hoyerová Klára
Published: June 2024

1

Ribosylated forms of plant hormones cytokinins (CKs) are the dominant CK species translocated at long distances. Their particular roles in plant physiology imply the existence of a yet uncharacterized CK riboside-specific membrane transport system. In this work, we report significant differences in the kinetics of the membrane transport of CK nucleobases and ribosides and the overall affinity of membrane-bound carriers towards the two CK forms. We show that CK ribosides can inhibit the uptake of CK nucleobases in tobacco Bright Yellow 2 cell suspensions but not vice versa, confirming the existence of a membrane transport system that strictly recognizes CK ribosides.

We further characterize the membrane transport of CK nucleobases and ribosides mediated by AtENT3 (EQULIBRATIVE NUCLEOSIDE TRANSPORTER 3), showing its preference towardstrans-zeatin riboside (tZR) over isopentenyl adenosine (iPR). With the molecular docking and molecular dynamics, we assess the interactions among the side chain of tZR and AtENT3 residues Tyr61 and Asp129, which are conserved in all AtENTs but not in the ENTs from non-plant species. Lastly, we show thatatent3mutation affects shoot phenotype, demonstrating the impact of CK riboside membrane transport on shoot development.
Transfer learning predicts species-specific drug interactions in emerging pathogens
Authors: Chung Carolina H. , Chang David C. , Rhoads Nicole M. , Shay Madeline R. , Srinivasan Karthik , Okezue Mercy A. , Brunaugh Ashlee D. , Chandrasekaran Sriram
Published: June 2024

Machine learning (ML) algorithms are necessary to efficiently identify potent drug combinations within a large candidate space to combat drug resistance. However, existing ML approaches cannot be applied to emerging and under-studied pathogens with limited training data. To address this, we developed a transfer learning and crowdsourcing framework (TACTIC) to train ML models on data from multiple bacteria. TACTIC was built using 2,965 drug interactions from 12 bacterial strains and outperformed traditional ML models in predicting drug interaction outcomes for species that lack training data. Top TACTIC model features revealed genetic and metabolic factors that influence cross- species and species-specific drug interaction outcomes. Upon analyzing ∼600,000 predicted drug interactions across 9 metabolic environments and 18 bacterial strains, we identified a small set of drug interactions that are selectively synergistic against Gram- negative (e.g.,A. baumannii) and non-tuberculous mycobacteria (NTM) pathogens. We experimentally validated synergistic drug combinations containing clarithromycin, ampicillin, and mecillinam againstM. abscessus, an emerging pathogen with growing levels of antibiotic resistance. Lastly, we leveraged TACTIC to propose selectively synergistic drug combinations to treat bacterial eye infections (endophthalmitis).
GnRH pulse generator activity in mouse models of polycystic ovary syndrome
Authors: Zhou Ziyue , Han Su Young , Pardo-Navarro Maria , Wall Ellen , Desai Reena , Vas Szilvia , Handelsman David J. , Herbison Allan E
Published: June 2024

One in ten women in their reproductive age suffer from polycystic ovary syndrome (PCOS) that, alongside subfertility and hyperandrogenism, typically presents with increased luteinizing hormone (LH) pulsatility. As such, it is suspected that the arcuate kisspeptin (ARNKISS) neurons that represent the GnRH pulse generator are dysfunctional in PCOS. We used herein vivoGCaMP fiber photometry and other approaches to examine the behavior of the GnRH pulse generator in two mouse models of PCOS. We began with the peripubertal androgen (PPA) mouse model of PCOS but found that it had a reduction in the frequency of ARNKISSneuron synchronization events (SEs) that drive LH pulses. Examining the prenatal androgen (PNA) model of PCOS, we observed highly variable patterns of pulse generator activity with no significant differences detected in ARNKISSneuron SEs, pulsatile LH secretion, or serum testosterone, estradiol, and progesterone concentrations. However, an unsupervised machine learning approach identified that the ARNKISSneurons of acyclic PNA mice continued to exhibit cyclical patterns of activity similar to that of normal mice. The frequency of ARNKISSneuron SEs was significantly increased in algorithm-identified “diestrous stage” PNA mice compared to controls. In addition, ARNKISSneurons exhibited reduced feedback suppression to progesterone in PNA mice and their pituitary gonadotrophs were also less sensitive to GnRH. These observations demonstrate the importance of understanding GnRH pulse generator activity in mouse models of PCOS. The existence of cyclical GnRH pulse generator activity in the acyclic PNA mouse indicates the presence of a complex phenotype with deficits at multiple levels of the hypothalamo-pituitary-gonadal axis.
CSPG4-targeting CAR-macrophages inhibit melanoma growth
Authors: Greiner Daniel , Xue Qian , Waddell Trinity QA , Kurudza Elena , Belote Rachel L , Dotti Gianpietro , Judson-Torres Robert L , Reeves Melissa Q , Cheshier Samuel H , Roh-Johnson Minna
Published: June 2024

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematological malignancies but has been clinically less effective in solid tumors. Engineering macrophages with CARs has emerged as a promising approach to overcome some of the challenges faced by CAR-T cells due to the macrophage’s ability to easily infiltrate tumors, phagocytose their targets, and reprogram the immune response. We engineered CAR-macrophages (CAR-Ms) to target chondroitin sulfate proteoglycan 4 (CSPG4), an antigen expressed in melanoma, and several other solid tumors. CSPG4-targeting CAR-Ms exhibited specific phagocytosis of CSPG4-expressing melanoma cells. Combining CSPG4-targeting CAR-Ms with CD47 blocking antibodies synergistically enhanced CAR-M-mediated phagocytosis and effectively inhibited melanoma spheroid growth in 3D. Furthermore, CSPG4-targeting CAR-Ms inhibited melanoma tumor growth in mouse models. These results suggest that CSPG4-targeting CAR-M immunotherapy is a promising solid tumor immunotherapy approach for treating melanoma.

STATEMENT OF SIGNIFICANCE

We engineered macrophages with CARs as an alternative approach for solid tumor treatment. CAR-macrophages (CAR-Ms) targeting CSPG4, an antigen expressed in melanoma and other solid tumors, phagocytosed melanoma cells and inhibited melanoma growthin vivo. Thus, CSPG4-targeting CAR-Ms may be a promising strategy to treat patients with CSPG4-expressing tumors.
Nanofibrous Wound Dressing with a Smart Drug Delivery System: Poly(N-Isopropylacrylamide)-Conjugated Polycaprolactone Nanofibers Loaded with Curcumin
Authors: Khan Dawood , Jyoti Anirban , Aliaa Nik , Patel Kapil D. , Tan Renjian , Kim Hae-Won , Chau David , Nguyen Linh
Published: June 2024

In response to clinical demands for advanced wound dressings, a "smart bandage" was developed by combining polycaprolactone (PCL) nanofibers and the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAAm). This bandage incorporates curcumin, an anti-inflammatory and antioxidant agent, to enhance wound healing. The LCST of PNIPAAm (32°C) enables an "on-off" drug delivery system, transitioning from a hydrophilic coil to a hydrophobic state. The nanofiber matrix was characterized using FTIR spectroscopy, SEM, water contact angle, and dynamic mechanical analysis. Curcumin release was assessed both above and below the LCST. The bandage is comfortable, easy to apply and remove, and promotes rapid wound healing. In vitro studies confirmed its non-toxicity to human dermal fibroblast cells. This "smart bandage" represents a significant advancement in wound care, with the potential to meet clinical requirements and enhance patient compliance, offering controlled drug delivery combined with the therapeutic benefits of curcumin.
Hippocampal volumes in UK Biobank are associated with APOE only in older adults
Authors: Chaloemtoem Ariya , Thornton Vera , Chang Yoonhoo , Anokhin Andrey P. , Belloy Michaël E. , Bijsterbosch Janine , Gordon Brian A. , Hartz Sarah M. , Bierut Laura J.
Published: June 2024

INTRODUCTION

The hippocampus atrophies with age and is implicated in neurodegenerative disorders including Alzheimer’s disease (AD). We examined the interplay between age andAPOEgenotype on total hippocampal volume.

METHODS

Utilizing neuroimaging data from 37,463 UK Biobank participants, we applied linear regression to quantify the association of age andAPOEwith hippocampal volume and identified the age when volumes of ε2/ε3, ε3/ε4, and ε4/ε4 carriers significantly deviated from ε3/ε3 using generalized additive modeling.

RESULTS

Total hippocampal volume declined with age, with significant differences byAPOEgenotype emerging after age 60. ε3/ε4 and ε4/ε4 carriers displayed reduced volumes from ages 69 and 61, respectively, while ε2/ε3 showed delayed decline starting at age 76.

DISCUSSION

The association ofAPOEand hippocampal volume is age-dependent, with differences in volumes of ε4/ε4 carriers detected as early as age 61. This work underscores the importance ofAPOEgenotype in determining when to begin screening for AD.
Healthcare providers’ knowledge and use of psychological and psychoSOCIAL screening and interventions in the management of patients with tendinopathy: An International Survey of Practice
Authors: O’Neill Seth , English Laura , Mallows Adrian , Stubbs Carl , Stephens Gareth , Briggs-Price Sam , Kirwan Paul , Lee Matt , McAuliffe Sean , Kenyon Matt
Published: June 2024

Background

Psychological and psychosocial factors play an important role in the management of patients with musculoskeletal disorders. Currently, there is no information exploring how clinicians current practice is informed by these factors in the people with tendinopathy exists.

Objectives

To explore healthcare providers knowledge and use of psychological and social screening and interventions in the management of patients with tendinopathy

Methods

An online survey was developed by a group of tendon experts. The survey was disseminated via special interest groups, social networks and professional organisations internationally.

Results

The survey had 103 completed responses. The majority of respondents used the subjective, 53% (N=55), subjective and objective, 28%(n=29), or objective 6% (n=6) examination to screen for psychological factors using both verbal and nonverbal methods. Psychosocial factors were screened for during the subjective assessment by 75% (n=77) of respondents. A further 15% (n=15) screened during the subjective and objective combined whilst 5% (n=5) examined this factor in the objective assessment in isolation.

Psychological screening tools were used by 25% (n= 26) of respondents and psychosocial factors by 12% (n=12) of respondents.

Treatment typically comprised of individualised education, reassurance, addressing mal-adaptive behaviours and behaviour change. Confidence in assessment and treatment was mixed and clinicians identified a desire for more specific training and self-development.

Conclusion

The proportion of clinicians screening and measuring psychological and psychosocial factors in clinical practice is high, but few use validated tools due to a lack of time and confidence.

Implication for clinical practice

Clinicians commonly assess psychological and social factors during assessment of individuals with tendinopathy, as part of their subjective and objective assessments. It is unclear how successfully clinicians identify these factors during their assessments, as they rarely use validated screening tools.

Key message –

Clinicians and researchers should examine and modify: fear of movement, Negative pain beliefs, Maladaptive/avoidance behaviors, catastrophisation and Anxiety (psychological constructs) and Quality of life, work related constructs, sleep quality, education health literacy and social interactions(psychoSOCIAL constructs) during clinical or research work.

Training needs to be developed to improve clinician confidence when assessing and treating psychological and psychoSOCIAL factors in patients with tendinopathy

Further work is needed to examine the barriers and facilitators to the use of appropriate validated psychological and psychoSOCIAL tools in clinical care.
Validation of the GCS-Pupil scale in Traumatic Brain Injury Incremental prognostic performance of pupillary reactivity with GCS in the prospective observational cohorts CENTER-TBI and TRACK-TBI
Authors: Vreeburg Rick J.G. , van Leeuwen Florian D. , Manley Geoffrey T. , Yue John K. , Brennan Paul M. , Sun Xiaoying , Jain Sonia , van Essen Thomas A. , Peul Wilco C. , Maas Andrew I.R. , Menon David K. , Steyerberg Ewout W.
Published: June 2024

Objective

To compare the incremental prognostic value of pupillary reactivity as captured in the GCS-Pupils score (GCS-P) or added as separate variable to the Glasgow Coma Scale (GCS) in traumatic brain injury (TBI).

Methods

We analyzed patients enrolled between 2014 and 2018 in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI, n=3521) and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI, n=1439) cohorts. We used logistic regression to quantify the prognostic performances of GCS-P versus GCS according to Nagelkerke’s R2. Endpoints were mortality and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-4) at 6 months after injury. We estimated 95% confidence intervals with bootstrap resampling to summarize the improvement in prognostic capability.

Results

GCS as a linear score had a R2of 24% (95% confidence interval [CI] 17-30) and 30% (95%CI 17-43) for mortality and 29% (95%CI 25-34) and 38% (95%CI 29-47) for unfavorable outcome in CENTER-TBI and TRACK-TBI respectively. In the meta-analysis, pupillary reactivity as a separate variable improved the R2by an absolute value of 6% and 2% for mortality and unfavorable outcome (95%CI 4.0-7.7 and 1.2-3.0, respectively), with half the improvement captured in the GCS-P score (3%, 95%CI 2.1-3.3 and 1%, 95%CI 1-1.7, respectively).

Conclusions

GCS-P has a stronger association with outcome after TBI than the GCS alone. However, for prognostic models, inclusion of GCS and pupillary reactivity as separate scores is preferable.
Mutation Pathogenicity Prediction by a Biology Based Explainable AI Multi-Modal Algorithm
Authors: Kellerman Raizy , Nayshool Omri , Barel Ortal , Paz Sharon , Amariglio Ninette , Klang Eyal , Rechavi Gideon
Published: June 2024

Most known pathogenic mutations occur in protein-coding regions of DNA and change the way proteins are made. Deciphering the protein structure therefore provides great insight into the molecular mechanisms underlying biological functions in human disease. While there have recently been major advances in the artificial intelligence-based prediction of protein structure, the determination of the biological and clinical relevance of specific mutations is not yet up to clinical standards. This challenge is of utmost medical importance when decisions, as critical as suggesting termination of pregnancy or recommending cancer-directed rational drugs, depend on the accuracy of prediction of the effect of the specific mutation. Currently, available tools are aiming to characterize the effect of a mutation on the functionality of the protein according to biochemical criteria, independent of the biological context. A specific change in protein structure can result either in loss of function (LOF) or gain-of-function (GOF) and the ability to identify the directionality of effect needs to be taken into consideration when interpreting the biological outcome of the mutation. Here we describeTriple-modalitiesVariant Interpretation andAnalysis (TriVIAI), a tool incorporating three complementing modalities for improved prediction of missense mutations pathogenicity: protein language model (pLM), graph neural network (GNN) and a tabular model incorporating physical properties from the protein structure. The TriVIAl ensemble’s predictions compare favorably with the existing tools across various metrics, achieving an AUC-ROC of 0.887, a precision-recall curve (PRC) score of 0.68, and a Brier score of 0.16. The TriVIAI ensemble is also endowed with two major advantages compared to other available tools. The first is the incorporation of biological insights which allow to differentiate between GOF mutations that tend to cluster in specific hotspots and affect structure in a specific functional way versus LOF mutations that are usually dispersed and can cripple the protein in a variety of different ways. Importantly, the advantage over other available tools is more noticeable with GOF mutations as their effect on the protein structure is less disruptive and can be misinterpreted by current variant prioritization strategies. Until now available AI-based pathogenicity predicting algorithms were a black box for the users. The second significant advantage of TriVIAI is the explainability of the ensemble which contrasts the other available AI-based pathogenicity predicting algorithms which constitute a black box for the users. This explainability feature is of major importance considering the clinical responsibility of the medical decision-makers using AI-based pathogenicity predictors.
Consistent Multi-Omic Relationships Uncover Molecular Basis of Pediatric Asthma IgE Regulation
Authors: Eicher Tara , Kelly Rachel S. , Braisted John , Siddiqui Jalal K. , Celedón Juan , Clish Clary , Gerszten Robert , Weiss Scott T. , McGeachie Michael , Machiraju Raghu , Lasky-Su Jessica , Mathé Ewy A.
Published: June 2024

Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma. To uncover these mechanisms using complementary metabolomic and transcriptomic data, abundance levels of 529 named metabolites and expression levels of 22,772 genes were measured among children with asthma in the Childhood Asthma Management Program (CAMP, N=564) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS, N=309) via the TOPMed initiative. Gene-metabolite associations dependent on IgE were identified within each cohort using multivariate linear models and were interpreted in a biochemical context using network topology, pathway and chemical enrichment, and representation within reactions. A total of 1,617 total IgE-dependent gene-metabolite associations from GACRS and 29,885 from CAMP met significance cutoffs. Of these, glycine and guanidinoacetic acid (GAA) were associated with the most genes in both cohorts, and the associations represented reactions central to glycine, serine, and threonine metabolism and arginine and proline metabolism. Pathway and chemical enrichment analysis further highlighted additional related pathways of interest. The results of this study suggest that GAA may modulate total IgE levels in two independent pediatric asthma cohorts with different characteristics, supporting the use of L-Arginine as a potential therapeutic for asthma exacerbation. Other potentially new targetable pathways are also uncovered.
Diagnostic Accuracy of Nanopore Sequencing for DetectingMycobacterium tuberculosisand Drug-Resistant Strains: A Systematic Review and Meta-Analysis
Authors: Carandang Timothy Hudson David Culasino , Cunanan Dianne Jaula , Co Gail S. , Pilapil John David , Garcia Juan Ignacio , Restrepo Blanca I. , Yotebieng Marcel , Torrelles Jordi B. , Notarte Kin Israel
Published: June 2024

Tuberculosis (TB), caused byMycobacterium tuberculosis(MTB) infection, remains a significant public health threat. The timeliness, portability, and capacity of nanopore sequencing for diagnostics can aid in early detection and drug susceptibility testing (DST), which is crucial for effective TB control. This study synthesized current evidence on the diagnostic accuracy of the nanopore sequencing technology in detecting MTB and its DST profile. A comprehensive literature search in PubMed, Scopus, MEDLINE, Cochrane, EMBASE, Web of Science, AIM, IMEMR, IMSEAR, LILACS, WPRO, HERDIN Plus, MedRxiv, and BioRxiv was performed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity, specificity, predictive values (PV), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated. Thirty-two studies were included; 13 addressed MTB detection only, 15 focused on DST only, and 4 examined both MTB detection and DST. No study used Flongle or PromethION. Seven studies were eligible for meta-analysis on MTB detection and five for DST; studies for MTB detection used GridION only while those for DST profile used MinION only. Our results indicate that GridION device has high sensitivity [88.61%; 95% CI (83.81–92.12%)] and specificity [93.18%; 95% CI (85.32–96.98%)], high positive predictive value [94.71%; 95% CI (89.99–97.27%)], moderately high negative predictive value [84.33%; 95% CI (72.02–91.84%)], and excellent DOR [107.23; 95% CI (35.15–327.15)] and AUC (0.932) in detecting MTB. Based on DOR and AUC, the MinION excelled in detecting pyrazinamide and rifampicin resistance; however, it underperformed in detecting isoniazid and ethambutol resistance. Additional studies will be needed to provide more precise estimates for MinION’s sensitivity in detecting drug-resistance, as well as DOR in detecting resistance to pyrazinamide, streptomycin, and ofloxacin. Studies on detecting resistance to bedaquiline, pretomanid, and linezolid are lacking.
Exploring the Gender Gap in Young Adult Mental Health during COVID-19: Evidence from the UK
Authors: Webster Mhairi , Manoukian Sarkis , McKendrick John H. , Biosca Olga
Published: June 2024

Aims

To explore the prevalence of a mental health gender gap within a young adult sample during the COVID-19 pandemic, and to identify the impact of loneliness and domestic time use on young people’s, and particularly young women’s mental health.

Method

Using data from the UK Longitudinal Household Survey (UKHLS), this research examines mental health prior to the pandemic (2019) and during the pandemic (April 2020 until September 2021). A random-effects regression analysis was conducted to examine the effects of loneliness, and domestic factors across age and gender to ascertain their contribution to the mental health gender gap in a young adult population.

Results

Average mental health decline was consistently higher for women compared to men, and young people (ages 16-24) saw a reduction in mental health twice as much as those in the oldest age category (over 65). Loneliness accounted for a share of the mental health gender gap, and a more decrease in mental health was recorded for young women experiencing loneliness, compared to older age groups. Domestic and familial factors did not have a significant impact on young people’s mental health.

Conclusions

Although across all ages and genders, mental health had returned to near pre-pandemic levels by September 2021, young people and especially women continue to have worse mental health compared to other age groups, which is consistent with pre-COVID age and gender inequalities. Loneliness is a key driver in gendered mental health inequalities during the pandemic in a young adult population.
Evaluating the Analytical Performance of Direct-to-Consumer Gut Microbiome Testing Services
Authors: Servetas Stephanie L. , Hoffmann Diane , Ravel Jacques , Jackson Scott A.
Published: June 2024

Consumer interest in personal microbiome health has given rise to numerous direct-to-consumer (DTC) microbiome testing services despite questions regarding their analytical and clinical validity, and consumer safety. These tests straddle the line between more strictly regulated medical devices and minimally regulated general health and wellness products; a distinction that may not be readily apparent to consumers. To assess the current state of the industry, we evaluated the performance of seven commercial DTC gut microbiome testing services using a standardized NIST - developed human fecal material. Our results reveal major discrepancies, both within and across the different service providers. Significantly, we found variability between providers was on the same scale as biological variability between different donors. We attribute the observed differences to methodological variability and lack of sufficient quality control. Additionally, we highlight that analytical performance is a prerequisite for making sound clinical recommendations. Our results demonstrate the need for standards to ensure analytical validity and regulatory oversight to ensure patient safety.
N-Cadherin mediated cell rearrangements shape embryonic macrophage cluster
Authors: Hasenauer Jacob , Meng Xiang , Scarborough Honor , Stanley-Ahmed Jasmine A. , Köster Darius Vasco , Ratheesh Aparna
Published: June 2024

Drosophila embryonic macrophages are highly motile phagocytic and secretory cells which are essential for embryonic development. Embryonic migration and dispersal of these cells along pre-determined routes is invariably tied to their functions such that misrouting or delay in macrophage migration has serious consequences for embryogenesis and adult homeostasis. In this study, we describe early steps of macrophage migration from their site of origin in the head mesoderm to the germband and show that hemocytes start moving as an epithelial-like cluster with N-Cadherin based Adherens junctions. The cells within the cluster move in a co-ordinated manner and exhibit cell rearrangements mediated through junction shrinkage. We found that N-Cadherin is dynamically relocalized during cluster extension and modulating N-Cadherin levels results in hemocyte dispersal away from their main axis of migration which affects migration into the germband. We therefore elucidate a novel multi-tiered mechanism which ensures that macrophages are positioned appropriately to regulate their distribution in the embryo.
Characterizing Public Sentiments and Drug Interactions during COVID-19: A Pretrained Language Model and Network Analysis of Social Media Discourse
Authors: Li Wanxin , Hua Yining , Zhou Peilin , Zhou Li , Xu Xin , Yang Jie
Published: June 2024

Objective

Harnessing drug-related data posted on social media in real time can offer insights into how the pandemic impacts drug use and monitor misinformation. This study developed a natural language processing (NLP) pipeline tailored for the analysis of social media discourse on COVID-19 related drugs.

Methods

This study constructed a full pipeline for COVID-19 related drug tweet analysis, utilizing pre-trained language model-based NLP techniques as the backbone. This pipeline is architecturally composed of four core modules: named entity recognition (NER) and normalization to identify medical entities from relevant tweets and standardize them to uniform medication names, target sentiment analysis (TSA) to reveal sentiment polarities associated with the entities, topic modeling to understand underlying themes discussed by the population, and drug network analysis to potential adverse drug reactions (ADR) and drug-drug interactions (DDI). The pipeline was deployed to analyze tweets related to COVID-19 and drug therapies between February 1, 2020, and April 30, 2022.

Results

From a dataset comprising 2,124,757 relevant tweets sourced from 1,800,372 unique users, our NER model identified the top five most-discussed drugs: Ivermectin, Hydroxychloroquine, Remdesivir, Zinc, and Vitamin D. Sentiment and topic analysis revealed that public perception was predominantly shaped by celebrity endorsements, media hotspots, and governmental directives rather than empirical evidence of drug efficacy. Co-occurrence matrices and complex network analysis further identified emerging patterns of DDI and ADR that could be critical for public health surveillance like better safeguarding public safety in medicines use.

Conclusion

This study evidences that an NLP-based pipeline can be a robust tool for large-scale public health monitoring and can offer valuable supplementary data for traditional epidemiological studies concerning DDI and ADR. The framework presented here aspires to serve as a cornerstone for future social media-based public health analytics.
Spin–spin interaction and magnetic Feshbach resonances in collisions of high-spin atoms with closed-shell atoms
Authors: Frye Matthew D. , Żuchowski Piotr S. , Tomza Michał
Published: June 2024

We investigate interactions and ultracold collisions of high-spin but spherical atoms with closed-shell atoms, focusing on the example of Cr with Yb. Such a combination has only one potential energy curve but gives rise to a substantial intra-atomic spin–spin interaction, which causes Feshbach resonances due to rotationally excited states. We find such resonances are guaranteed below 250 G and can reach widths of tens of G in favorable circumstances. We study the effect of hyperfine structure, which can create additional wide resonances at low fields. Finally, we consider isotopic substitution and show that for any realistic potential it is very likely that at least one combination of commonly used isotopes will have resonances with experimentally favorable properties. Thus, this is a promising system for both molecule formation and studying quantum mixtures including dipolar species.

Published by the American Physical Society
2024