bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision health equity for racialized communities
Authors: Valiani Arafaat A. , Anderson David , Gonzales Angela , Gray Mandi , Hardcastle Lorian , Turin Tanvir C. 
Published: December 2023

AbstractIn the last three decades, a cohort of genomicists have intentionally sought to include more racially diverse people in their research in human genomics and precision medicine. How such efforts to be inclusive in human genomic research and precision medicine are modeled and enacted, specifically if the terms of inclusion are equitable for these communities remains to be explored. In this commentary, we review the historical context in which issues of racial inclusion arose with early genome and genetics projects. We then discuss attempts to include racialized peoples in more recent human genomics research. In conclusion, we raise critical issues to consider in the future of equitable human genomics and precision medicine research involving racialized communities, particularly as it concerns working towards what we callPrecision Health Equity(PHE).Specifically, we examine issues of genetic data governance and the terms of participation in inclusive human genomics and precision health research. We do so by drawing on insights and protocols developed by researchers investigating Indigenous Data Sovereignty and propose exploring their application and adaptation to precision health research involving racialized communities.
Peripheral signaling pathways contributing to non-histaminergic itch in humans
Authors: Fiebig Andrea , Leibl Victoria , Oostendorf David , Lukaschek Saskia , Frömbgen Jens , Masoudi Maral , Kremer Andreas E. , Strupf Marion , Reeh Peter , Düll Miriam , Namer Barbara 
Published: December 2023

Abstract

Background
Chronic itch (chronic pruritus) is a major therapeutic challenge that remains poorly understood despite the extensive recent analysis of human pruriceptors. It is unclear how the peripheral nervous system differentiates the signaling of non-histaminergic itch and pain.

Methods
Here we used psychophysical analysis and microneurography (single nerve fiber recordings) in healthy human volunteers to explore the distinct signaling mechanisms of itch, using the pruritogens β-alanine, BAM 8-22 and cowhage extract.

Results
The mode of application (injection or focal application using inactivated cowhage spicules) influenced the itch/pain ratio in sensations induced by BAM 8-22 and cowhage but not β-alanine. We found that sensitizing pre-injections of prostaglandin E2 increased the pain component of BAM 8-22 but not the other pruritogens. A-fibers contributed only to itch induced by β-alanine. TRPV1 and TRPA1 were necessary for itch signaling induced by all three pruritogens. In single-fiber recordings, we found that BAM 8-22 and β-alanine injection activated nearly all CM-fibers (to different extents) but not CMi-fibers, whereas cowhage extract injection activated only 56% of CM-fibers but also 25% of CMi-fibers. A “slow bursting discharge pattern” was evoked in 25% of CM-fibers by β-alanine, in 35% by BAM 8-22, but in only 10% by cowhage extract.

Conclusion
Our results indicate that no labeled line exists for these pruritogens in humans. A combination of different mechanisms, specific for each pruritogen, leads to itching sensations rather than pain. Notably, non-receptor-based mechanisms such as spatial contrast or discharge pattern coding seem to be important processes. These findings will facilitate the discovery of therapeutic targets for chronic pruritus, which are unlikely to be treated effectively by single receptor blockade.
Bridging gaps: a qualitative inquiry on improving paediatric rheumatology care among healthcare workers in Kenya
Authors: Migowa Angela , Bernatsky Sasha , Ngugi Anthony K. , Foster Helen E. , Muriuki Peterrock , Riang’a Roselyter M. , Luchters Stanley 
Published: December 2023

Abstract
Background
Due to the paucity of paediatric rheumatologists in Kenya, it is paramount that we explore strategies to bridge clinical care gaps for paediatric rheumatology patients in order to promote early diagnosis, prompt referral, and optimal management.

Purpose
To identify proposed interventions which can improve the ability of non-specialist healthcare workers to care for paediatric rheumatology patients across Kenya.

Methods
We conducted 12 focus group discussions with clinical officers (community physician assistants), nurses, general practitioners and paediatricians across six regions in Kenya. Interviews were conducted, audio-recorded, transcribed verbatim, and analysed using MAXQDA 2022.2 software.

Results
A total of 68 individuals participated in the study; 11 clinical officers, 12 nurses, 10 general practitioners, 27 paediatricians and eight other healthcare workers. Proposed patient interventions included patient education and psychosocial support. Community interventions were outreach awareness campaigns, mobilising financial support for patients’ care, mobilising patients to access diagnostic and therapeutic interventions. Healthcare worker interventions include diagnostic, management, and referral guidelines, as well as research and educational interventions related to symptom identification, therapeutic strategies, and effective patient communication skills. In addition, it was highlighted that healthcare systems should be bolstered to improve insurance coverage and access to integrated multi-disciplinary clinical care.

Conclusions
Study participants were able to identify potential initiatives to improve paediatric rheumatology care in Kenya. Additional efforts are underway to design, implement and monitor the impact of some of these potential interventions,
The effect of metformin on senescence of T lymphocytes
Authors: Yang Jia , Liu Hai-Cheng , Zhang Jian-Qing , Zou Jian-Yong , Zhang Xin , Chen Wo-Ming , Gu Yong , Hong Hai 
Published: December 2023

Abstract
Background
Immunosenescence occurs as people age, leading to an increased incidence of age-related diseases. The number of senescent T cells also rises with age. T cell senescence and immune response dysfunction can result in a decline in immune function, especially in anti-tumor immune responses. Metformin has been shown to have various beneficial effects on health, such as lowering blood sugar levels, reducing the risk of cancer development, and slowing down the aging process. However, the immunomodulatory effects of metformin on senescent T cells still need to be investigated.

Methods
PBMCs isolation from different age population (n = 88); Flow Cytometry is applied to determine the phenotypic characterization of senescent T lymphocytes; intracellular staining is applied to determine the function of senescent T cells; Enzyme-Linked Immunosorbent Assay (ELISA) is employed to test the telomerase concentration. The RNA-seq analysis of gene expression associated with T cell senescence.

Results
The middle-aged group had the highest proportion of senescent T cells. We found that metformin could decrease the number of CD8 + senescent T cells. Metformin affects the secretion of SASP, inhibiting the secretion of IFN-γ in CD8 + senescent T cells. Furthermore, metformin treatment restrained the production of the proinflammatory cytokine IL-6 in lymphocytes. Metformin had minimal effects on Granzyme B secretion in senescent T cells, but it promoted the production of TNF-α in senescent T cells. Additionally, metformin increased the concentration of telomerase and the frequency of undifferentiated T cells. The results of RNA-seq showed that metformin promoted the expression of genes related to stemness and telomerase activity, while inhibiting the expression of DNA damage-associated genes.

Conclusion
Our findings reveal that metformin could inhibit T cell senescence in terms of cell number, effector function, telomerase content and gene expression in middle-aged individuals, which may serve as a promising approach for preventing age-related diseases in this population.
The impact of lesion side on bilateral upper limb coordination after stroke
Authors: Shih Pei-Cheng , Steele Christopher J. , Hoepfel Dennis , Muffel Toni , Villringer Arno , Sehm Bernhard 
Published: December 2023

Abstract
Background
A stroke frequently results in impaired performance of activities of daily life. Many of these are highly dependent on effective coordination between the two arms. In the context of bimanual movements, cyclic rhythmical bilateral arm coordination patterns can be classified into two fundamental modes: in-phase (bilateral homologous muscles contract simultaneously) and anti-phase (bilateral muscles contract alternately) movements. We aimed to investigate how patients with left (LHS) and right (RHS) hemispheric stroke are differentially affected in both individual-limb control and inter-limb coordination during bilateral movements.

Methods
We used kinematic measurements to assess bilateral coordination abilities of 18 chronic hemiparetic stroke patients (9 LHS; 9 RHS) and 18 age- and sex-matched controls. Using KINARM upper-limb exoskeleton system, we examined individual-limb control by quantifying trajectory variability in each hand and inter-limb coordination by computing the phase synchronization between hands during anti- and in-phase movements.

Results
RHS patients exhibited greater impairment in individual- and inter-limb control during anti-phase movements, whilst LHS patients showed greater impairment in individual-limb control during in-phase movements alone. However, LHS patients further showed a swap in hand dominance during in-phase movements.

Conclusions
The current study used individual-limb and inter-limb kinematic profiles and showed that bilateral movements are differently impaired in patients with left vs. right hemispheric strokes. Our results demonstrate that both fundamental bilateral coordination modes are differently controlled in both hemispheres using a lesion model approach. From a clinical perspective, we suggest that lesion side should be taken into account for more individually targeted bilateral coordination training strategies.
Trial registration: the current experiment is not a health care intervention study.
Epidemiological surveillance of respiratory viral infections in SARS-CoV-2-negative samples during COVID-19 pandemic in Iran
Authors: Maleki Ali , Mehrbod Parvaneh , Bokharaei-Salim Farah , Eybpoosh Sana , Tavakoli Mahsa , Mohammadnejad Azita Eshratkhah , Hosseini Zahra , Kashanian Setareh , Asadi Laya Farhan , Salehi-Vaziri Mostafa , Fotouhi Fatemeh 
Published: December 2023

Abstract
Background
To improve the patient care, public health surveillance, and infection control, it is crucial to identify the presence and frequency of the common respiratory infections in individuals with COVID-19 symptoms but tested negative for SARS-CoV-2. This study aimed to shed light on this during the COVID-19 pandemic in Iran.

Methods
In this cross-sectional study, a total of 1,002 patients with acute respiratory infection who had negative SARS-CoV-2 test results and referred to Valfajr Health Center, the National Collaborating Laboratory of Influenza and COVID-19 National Reference Laboratory at Pasteur Institute of Iran were recruited between January 2020 and January 2022. Nasopharyngeal and oropharyngeal swab samples were collected to detect 17 common respiratory viruses via TaqMan one-step real-time multiplex PCR. Demographic and clinical data of the participants were obtained from their electronic medical records.

Results
In total, 218 samples (21.8%) were tested positive for at least one respiratory virus infection. Most of the common investigated respiratory viruses belonged to the years 2020 and 2022. The number of investigated patients in 2021 was few, which highlights the impact of health measures following the COVID-19 pandemic in Iran. Influenza A was the most common virus (5.8%), while adenovirus had the lowest prevalence (0.1%). Although the rate of respiratory virus infection was higher in men (24%) compared to women (19.3%), this difference was not statistically significant (P = 0.069). The prevalence of respiratory viruses had an inverse association with increasing age, with the highest rate (55.6%) observed in the age group below 2 years and the lowest rate (12.7%) in those above 65 years.

Conclusion
Our findings underscore the significance of adopting a comprehensive approach to respiratory infections detection and management. These results can be employed for the development of syndromic surveillance systems and implementation of the effective infection control measures. Furthermore, the results contribute to better understanding of the dynamics of respiratory viruses, both during pandemic periods and in non-pandemic contexts.
Apoptosis is mediated by FeHV-1 through the intrinsic pathway and interacts with the autophagic process
Authors: Ferrara Gianmarco , Longobardi Consiglia , Sgadari Maria Francesca , Restucci Brunella , Iovane Giuseppe , Ciarcia Roberto , Pagnini Ugo , Montagnaro Serena 
Published: December 2023

Abstract
Background
Although FeHV-1 is a primary feline pathogen, little is known about its interactions with host cells. Its relationship with several cellular pathways has recently been described, whereas its interplay with the apoptotic process, unlike other herpesviruses, has not yet been clarified. The aim of this work was to evaluate whether FeHV-1 induces apoptosis in its permissive cells, as well as the pathway involved and the effects of induction and inhibition of apoptosis on viral replication.

Methods
Monolayers of CRFK cells were infected at different times with different viral doses. A cytofluorimetric approach allowed the quantification of cells in early and late apoptosis. All infections and related controls were also subjected to Western blot analysis to assess the expression of apoptotic markers (caspase 3-8-9, Bcl-2, Bcl-xL, NF-κB). An inhibitor (Z-VAD-FMK) and an inducer (ionomycin) were used to evaluate the role of apoptosis in viral replication. Finally, the expression of autophagy markers during the apoptosis inhibition/induction and the expression of apoptosis markers during autophagy inhibition/induction were evaluated to highlight any crosstalk between the two pathways.

Results
FeHV-1 triggered apoptosis in a time- and dose-dependent manner. Caspase 3 cleavage was evident 48 h after infection, indicating the completeness of the process at this stage. While caspase 8 was not involved, caspase 9 cleavage started 24 h post-infection. The expression of other mitochondrial damage markers also changed, suggesting that apoptosis was induced via the intrinsic pathway. NF- κB was up-regulated at 12 h, followed by a gradual decrease in levels up to 72 h. The effects of apoptosis inhibitors and inducers on viral replication and autophagy were also investigated. Inhibition of caspases resulted in an increase in viral glycoprotein expression, higher titers, and enhanced autophagy, whereas induction of apoptosis resulted in a decrease in viral protein expression, lower viral titer, and attenuated autophagy. On the other hand, the induction of autophagy reduced the cleavage of caspase 3.

Conclusions
In this study, we established how FeHV-1 induces the apoptotic process, contributing to the understanding of the relationship between FeHV-1 and this pathway.
Maternal health outcomes in the context of fragility: a retrospective study from Lebanon
Authors: Dimassi Hani , Alameddine Mohamad , Sabra Nadine , El Arnaout Nour , Harb Ranime , Hamadeh Randa , El Kak Faysal , Shanaa Abed , Mossi Marta Orozco , Saleh Shadi , AlArab Natally 
Published: December 2023

Abstract
Background and aims
The Lebanese healthcare system faces multiple challenges including limited capacities, shortage of skilled professionals, and inadequate supplies, in addition to hosting a significant number of refugees. While subsidized services are available for pregnant women, representing the majority of the refugee population in Lebanon, suboptimal access to antenatal care (ANC) and increased maternal mortality rates are still observed, especially among socioeconomically disadvantaged populations. This study aimed to review the maternal health outcomes of disadvantaged Lebanese and refugee pregnant women seeking ANC services at primary healthcare centers (PHCs) in Lebanon.

Methods
A retrospective chart review was conducted at twenty PHCs in Lebanon, including Ministry of Public Health (MOPH) and United Nations Relief and Works Agency for Palestine refugees (UNRWA) facilities. Data was collected from medical charts of pregnant women who visited the centers between August 2018 and August 2020. Statistical analysis was performed to explore outcomes such as the number of ANC visits, delivery type, and onset of delivery, using bivariate and multivariable logistic regression models.

Results
In the study, 3977 medical charts were analyzed. A multivariate logistic regression analysis, revealed that suboptimal ANC visits were more common in the Beqaa region and among women with current abortion or C-section. Syrians had reduced odds of C-sections, and Beqaa, Mount Lebanon, and South Lebanon regions had reduced odds of abortion. Suboptimal ANC visits and history of C-section increased the odds of C-section and abortion in the current pregnancy. As for preterm onset, the study showed an increased likelihood for it to occur when being Palestinian, having current C-section delivery, experiencing previous preterm onset, and enduring complications at the time of delivery.

Conclusion
This study suggests the need for low-cost interventions aiming at enhancing access to ANC services, especially among pregnant women in fragile settings.
Development and characterization of NILK-2301, a novel CEACAM5xCD3 κλ bispecific antibody for immunotherapy of CEACAM5-expressing cancers
Authors: Seckinger Anja , Majocchi Sara , Moine Valéry , Nouveau Lise , Ngoc Hoang , Daubeuf Bruno , Ravn Ulla , Pleche Nicolas , Calloud Sebastien , Broyer Lucile , Cons Laura , Lesnier Adeline , Chatel Laurence , Papaioannou Anne , Salgado-Pires Susana , Krämer Sebastian , Gockel Ines , Lordick Florian , Masternak Krzysztof , Poitevin Yves , Magistrelli Giovanni , Malinge Pauline , Shang Limin , Kallendrusch Sonja , Strein Klaus , Hose Dirk 
Published: December 2023

Abstract
Background
T-cell retargeting to eliminate CEACAM5-expressing cancer cells via CEACAM5xCD3 bispecific antibodies (BsAbs) showed limited clinical activity so far, mostly due to insufficient T-cell activation, dose-limiting toxicities, and formation of anti-drug antibodies (ADA).

Methods
We present here the generation and preclinical development of NILK-2301, a BsAb composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format).

Results
NILK-2301 binds CD3ɛ on T-cells with its lambda light chain arm with an affinity of ≈100 nM, and the CEACAM5 A2 domain on tumor cells by its kappa light chain arm with an affinity of ≈5 nM. FcγR-binding is abrogated by the “LALAPA” mutation (Leu234Ala, Leu235Ala, Pro329Ala). NILK-2301 induced T-cell activation, proliferation, cytokine release, and T-cell dependent cellular cytotoxicity of CEACAM5-positive tumor cell lines (5/5 colorectal, 2/2 gastric, 2/2 lung), e.g., SK-CO-1 (Emax = 89%), MKN-45 (Emax = 84%), and H2122 (Emax = 97%), with EC50 ranging from 0.02 to 0.14 nM. NILK-2301 binds neither to CEACAM5-negative or primary colon epithelial cells nor to other CEACAM family members. NILK-2301 alone or in combination with checkpoint inhibition showed activity in organotypic tumor tissue slices and colorectal cancer organoid models. In vivo, NILK-2301 at 10 mg/kg significantly delayed tumor progression in colon- and a pancreatic adenocarcinoma model. Single-dose pharmacokinetics (PK) and tolerability in cynomolgus monkeys at 0.5 or 10 mg/kg intravenously or 20 mg subcutaneously showed dose-proportional PK, bioavailability ≈100%, and a projected half-life in humans of 13.1 days. NILK-2301 was well-tolerated. Data were confirmed in human FcRn TG32 mice.

Conclusions
In summary, NILK-2301 combines promising preclinical activity and safety with lower probability of ADA-generation due to its format compared to other molecules and is scheduled to enter clinical testing at the end of 2023.
The stromal microenvironment and ovarian aging: mechanisms and therapeutic opportunities
Authors: Shen Lu , Liu Junfeng , Luo Aiyue , Wang Shixuan 
Published: December 2023

AbstractFor decades, most studies of ovarian aging have focused on its functional units, known as follicles, which include oocytes and granulosa cells. However, in the ovarian stroma, there are a variety of somatic components that bridge the gap between general aging and ovarian senescence. Physiologically, general cell types, microvascular structures, extracellular matrix, and intercellular molecules affect folliculogenesis and corpus luteum physiology alongside the ovarian cycle. As a result of damage caused by age-related metabolite accumulation and external insults, the microenvironment of stromal cells is progressively remodeled, thus inevitably perturbing ovarian physiology. With the established platforms for follicle cryopreservation and in vitro maturation and the development of organoid research, it is desirable to develop strategies to improve the microenvironment of the follicle by targeting the perifollicular environment. In this review, we summarize the role of stromal components in ovarian aging, describing their age-related alterations and associated effects. Moreover, we list some potential techniques that may mitigate ovarian aging based on their effect on the stromal microenvironment.
Present and future are getting confused: are we equipped to face the technological revolution?
Authors: Perilongo Giorgio , Agostiniani Rino , Corsello Giovanni , Marseglia Gianluigi , Muraca Maurizio , Staiano Anna Maria , Zuccotti Gianvincenzo , Baraldi Eugenio ,   For the Commission of Technology Innovation in Pediatrics, Italian Society of Pediatrics
Published: December 2023

Abstract
Background
This is a commentary reporting the outcome of a workshop promoted by the Department of Woman’s and Child’s Health of the University of Padua (Italy) focused on the emerging issue of what seems to be the increasing agemone role of technology.

Main body
Over the centuries, technology has always been at the service of science, with theoretical insights anticipating experimental proofs. Over the last decades, however, the situation has radically changed, due to several factors. Technology seems to be playing an agemone role. The present and notably the future generation of scientists have major challenges to face. They have to deal with the forces generated by the infosphera; to dominate the technology and to maintain the capacity of generating inquisitive, creative, ethical and spiritual thoughts capable of addressing new scientific hypotheses and projects directed to the individual and collective good. However, in this scenario, what seems more relevant is to focus all our efforts in preparing ourselves, first, and then the new generations to face these challenges. From this point of view, the academic institutions and the scientific societies, have a major responsibility to deal with.

Conclusions
The academic ecosystem traditionally used to educate the new generation of professionals as well as, and most importantly, the cultural, the professional pathways presently used to form them need to be extensively revised. The time is running short and the stakes are high. The debate is open.