bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial effects of GABA-producing potential probiotic Limosilactobacillus fermentum L18 of human origin on intestinal permeability and human gut microbiota
Authors: Kaur Sumanpreet , Sharma Preeti , Mayer Melinda J. , Neuert Saskia , Narbad Arjan , Kaur Sukhraj
Published: December 2023

Background

Gamma-aminobutyric acid (GABA) is a non-protein amino acid with neuroinhibitory, antidiabetic, and antihypertensive properties and is used as a drug for treating anxiety and depression. Some strains of lactobacilli are known to produce GABA and strengthen the gut barrier function which play an important role in ameliorating the effects caused by the pathogen on the gut barrier. The probiotic bacteria are also known to modulate the human fecal microbiota, however, the role of GABA-producing strains on the gut epithelium permeability and gut microbiota is not known.

Results

In this study, we report the production of high levels of GABA by potential probiotic bacterium Limosilactobacillus fermentum L18 for the first time. The kinetics of the production of GABA by L18 showed that the maximum production of GABA in the culture supernatant (CS) occurred at 24 h, whereas in fermented milk it took 48 h of fermentation. The effect of L18 on the restoration of lipopolysaccharide (LPS)-disrupted intestinal cell membrane permeability in Caco-2 monolayers showed that it significantly restored the transepithelial electrical resistance (TEER) values, by significantly increasing the levels of junction proteins, occludin and E-cadherin in L18 and LPS-treated Caco-2 cells as compared to only LPS-treated cells. The effect of GABA-secreting L18 on the metataxonome of human stool samples from healthy individuals was investigated by a batch fermentor that mimics the conditions of the human colon. Although, no differences were observed in the α and β diversities of the L18-treated and untreated samples at 24 h, the relative abundances of bacterial families Lactobacillaceae and Bifidobacteriaceae increased in the L18-treated group, but both decreased in the untreated groups. On the other hand, the relative abundance of Enterobacteriaceae decreased in the L18 samples but it increased in the untreated samples.

Conclusion

These results indicate that Li. fermentum L18 is a promising GABA-secreting strain that strengthens the gut epithelial barrier by increasing junction protein concentrations and positively modulating the gut microbiota. It has the potential to be used as a psychobiotic or for the production of functional foods for the management of anxiety-related illnesses.
Precision health equity for racialized communities
Authors: Valiani Arafaat A. , Anderson David , Gonzales Angela , Gray Mandi , Hardcastle Lorian , Turin Tanvir C.
Published: December 2023

In 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

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

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

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

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

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

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

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

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

For 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

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.
Pre-operative clonal hematopoiesis is related to adverse outcome in lung cancer after adjuvant therapy
Authors: Yun Jae Kwang , Kim Sugyeong , An Hongyul , Lee Geun Dong , Kim Hyeong Ryul , Kim Yong-Hee , Kim Dong Kwan , Park Seung-Il , Choi Sehoon , Koh Youngil
Published: December 2023

Background

Clonal hematopoiesis (CH) frequently progresses after chemotherapy or radiotherapy. We evaluated the clinical impact of preoperative CH on the survival outcomes of patients with non-small cell lung cancer (NSCLC) who underwent surgical resection followed by adjuvant therapy.

Methods

A total of 415 consecutive patients with NSCLC who underwent surgery followed by adjuvant therapy from 2011 to 2017 were analyzed. CH status was evaluated using targeted deep sequencing of blood samples collected before surgery. To minimize the possible selection bias between the two groups according to CH status, a propensity score matching (PSM) was adopted. Early-stage patients were further analyzed with additional matched cohort of patients who did not receive adjuvant therapy.

Results

CH was detected in 21% (86/415) of patients with NSCLC before adjuvant therapy. Patients with CH mutations had worse overall survival (OS) than those without (hazard ratio [95% confidence interval] = 1.56 [1.07–2.28], p = 0.020), which remained significant after the multivariable analysis (1.58 [1.08–2.32], p = 0.019). Of note, the presence of CH was associated with non–cancer mortality (p = 0.042) and mortality of unknown origin (p = 0.018). In patients with stage IIB NSCLC, there was a significant interaction on OS between CH and adjuvant therapy after the adjustment with several cofactors through the multivariable analysis (HR 1.19, 95% CI 1.00–1.1.41, p = 0.041).

Conclusions

In resected NSCLC, existence of preoperative CH might amplify CH-related adverse outcomes through adjuvant treatments, resulting in poor survival results.
Effects of biofeedback on biomechanical factors associated with chronic ankle instability: a systematic review with meta-analysis
Authors: Mousavi Seyed Hamed , Khorramroo Fateme , Minoonejad Hooman , Zwerver Johannes
Published: December 2023

Background

Biofeedback may alter the biomechanics of lower extremities in patients with chronic ankle instability (CAI). We aimed to systematically review the literature on the effect of gait-training and biofeedback on biomechanical parameters in individuals with CAI and conduct a meta-analysis.

Methods

We searched four databases including PubMed, Web of Science, Scopus and Embase from their inception through 30th June 2022. The Downs and Black appraisal scale was applied to assess quality of included studies. Two reviewers screened studies to identify those reporting the effect of biofeedback on biomechanical factors associated with CAI. Outcomes of interest were kinetics and kinematics. Two authors separately extracted data from included studies. Data of interest were study design, number of sessions, intervention, tools, outcomes, number, sex, age, height, and body mass of participants.

Results

Thirteen studies with a total of 226 participants were included. Biofeedback was capable of shifting center of pressure (COP) and lateral plantar pressure medially and reducing foot inversion, adduction, propulsive vertical ground reaction force (vGRF), ankle joint contact force, peak pressure and pressure time integral in the lateral mid-foot and forefoot. Auditory biofeedback had agreater impact on modifying plantar pressure in individuals with CAI. The meta-analyses revealed that visual biofeedback reduces peak pressure in lateral mid-foot and pressure time integral at lateral and medial heel and pressure increases under the hallux.

Conclusion

Biofeedback can alter pressure, vGRF, and foot inversion associated with CAI. Auditory biofeedback had greater impact on modifying plantar pressure in individuals with CAI. Further studies are required to assess the prolonged effect and clinical consequences of biofeedback or a combination of feedback on CAI in different age groups. Moreover, developing a low-cost and user-friendly device that can be evaluated in high quality RCTs is important prior to implementing the intervention in the clinical setting to reduce symptoms of CAI.
Alterations in DNA methylation associate with reduced migraine and headache days after medication withdrawal treatment in chronic migraine patients: a longitudinal study
Authors: Mehta Divya , de Boer Irene , Sutherland Heidi G. , Pijpers Judith A. , Bron Charlene , Bainomugisa Charlotte , Haupt Larisa M. , van den Maagdenberg Arn M. J. M. , Griffiths Lyn R. , Nyholt Dale R. , Terwindt Gisela M.
Published: December 2023

Background

Chronic migraine, a highly disabling migraine subtype, affects nearly 2% of the general population. Understanding migraine chronification is vital for developing better treatment and prevention strategies. An important factor in the chronification of migraine is the overuse of acute headache medication. However, the mechanisms behind the transformation of episodic migraine to chronic migraine and vice versa have not yet been elucidated. We performed a longitudinal epigenome-wide association study to identify DNA methylation (DNAm) changes associated with treatment response in patients with chronic migraine and medication overuse as part of the Chronification and Reversibility of Migraine clinical trial. Blood was taken from patients with chronic migraine (n = 98) at baseline and after a 12-week medication withdrawal period. Treatment responders, patients with ≥ 50% reduction in monthly headache days (MHD), were compared with non-responders to identify DNAm changes associated with treatment response. Similarly, patients with ≥ 50% versus < 50% reduction in monthly migraine days (MMD) were compared.

Results

At the epigenome-wide significant level (p < 9.42 × 10–8), a longitudinal reduction in DNAm at an intronic CpG site (cg14377273) within the HDAC4 gene was associated with MHD response following the withdrawal of acute medication. HDAC4 is highly expressed in the brain, plays a major role in synaptic plasticity, and modulates the expression and release of several neuroinflammation markers which have been implicated in migraine pathophysiology. Investigating whether baseline DNAm associated with treatment response, we identified lower baseline DNAm at a CpG site (cg15205829) within MARK3 that was significantly associated with MMD response at 12 weeks.

Conclusions

Our findings of a longitudinal reduction in HDAC4 DNAm status associated with treatment response and baseline MARK3 DNAm status as an early biomarker for treatment response, provide support for a role of pathways related to chromatin structure and synaptic plasticity in headache chronification and introduce HDAC4 and MARK3 as novel therapeutic targets.
Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer’s disease and vascular dementia
Authors: Chua Xin Ying , Torta Federico , Chong Joyce R. , Venketasubramanian Narayanaswamy , Hilal Saima , Wenk Markus R. , Chen Christopher P. , Arumugam Thiruma V. , Herr Deron R. , Lai Mitchell K. P.
Published: December 2023

Background

Alzheimer’s disease (AD) and vascular dementia (VaD) are two of the commonest causes of dementia in the elderly. Of the myriad biomolecules implicated in dementia pathogenesis, sphingolipids have attracted relatively scant research attention despite their known involvement in multiple pathophysiological processes. The potential utility of peripheral sphingolipids as biomarkers in dementia cohorts with high concomitance of cerebrovascular diseases is also unclear.

Methods

Using a lipidomics platform, we performed a case–control study of plasma sphingolipids in a prospectively assessed cohort of 526 participants (non-cognitively impaired, NCI = 93, cognitively impaired = 217, AD = 166, VaD = 50) using a lipidomics platform.

Results

Distinct patterns of sphingolipid alterations were found in AD and VaD, namely an upregulation of d18:1 species in AD compared to downregulation of d16:1 species in VaD. In particular, GM3 d18:1/16:0 and GM3 d18:1/24:1 showed the strongest positive associations with AD. Furthermore, evaluation of sphingolipids panels showed specific combinations with higher sensitivity and specificity for classification of AD (Cer d16:1/24:0. Cer d18:1/16:0, GM3 d16:1/22:0, GM3 d18:1/16:0, SM d16:1/22:0, HexCer d18:1/18:0) and VAD (Cer d16:1/24:0, Cer d18:1/16:0, Hex2Cer d16:1/16:0, HexCer d18:1/18:0, SM d16:1/16:0, SM d16:1/20:0, SM d18:2/22:0) compared to NCI.

Conclusions

AD and VaD are associated with distinct changes of plasma sphingolipids, warranting further studies into underlying pathophysiological mechanisms and assessments of their potential utility as dementia biomarkers and therapeutic targets.
Plasmodium ovale infection in Sri Lanka: distant exposure and incidental detection of hyperparasitemia: a case report
Authors: Kularatne Damsara , Chulasiri Pubudu , Dharmapala Arinda , Kularatne Senanayake
Published: December 2023

Background

Plasmodium ovale malaria, which was previously endemic to tropical Africa and the Southwest Pacific islands is now being reported from parts of Asia. In Sri Lanka, the indigenous transmission of malaria has not been documented since October 2012. Since then, there have been several imported cases of malaria, including P.ovale, which have been detected sporadically. The reporting case of P. ovale was imported and detected incidentally in 2021, with several atypical presentations.

Case presentation

A 40-year-old Sri Lankan medical doctor developed continuous fever with chills, rigors, and dysuria a day following removal of a large lipoma at the root of the neck under general anaesthesia. When the fever has been responding to antibiotics, on the 4th postoperative day a mild thrombocytopenia on complete blood count was detected. A blood smear which was done on the 5th postoperative day incidentally found a malaria parasite and confirmed as Plasmodium ovale with a density of 6535 parasites/microliter on the same day. He never had malaria in the past, but he had worked in South Sudan 1 year ago and visited India six months ago. On the 6th postoperative day, he was treated with chloroquine, and hyperparasitemia reduced rapidly by the next day. As the fever recurred with clinical deterioration, he was treated with different antibiotics. During the course of the illness, he did not develop pallor, or icterus except for a palpable soft spleen. The parasite count was zero on the 9th postoperative day and his fever subsided on the next day. Further, he was treated with primaquine to prevent future relapse and transmission.

Conclusion

A long incubation period, incidental detection of P ovale in a blood smear, and hyperparasitaemia are the atypical presentations of this case. Postoperative bacterial infection and stress may have reactivated the dormant malaria (hyponozoites) in this patient with an unusual picture. Coinfection of malaria with bacterial sepsis is a challenge in the management of the patient. As the Anopheles mosquito vector exists in Sri Lanka, the risk of indigenous transmission is high from such imported cases of P. ovale.
Streptococcus ruminantium-associated sheep mastitis outbreak detected in Italy is distinct from bovine isolates
Authors: Rosa Maria Nives , Vezina Ben , Marogna Gavino , Canu Antonella , Molotzu Monica Rosaria , Tola Sebastiana
Published: December 2023

Streptococcus ruminantiumis the causative agent of several bovine and ovine diseases, however reports are uncommon and application of whole genome sequencing to identify is rare. We report for the first time, a severe ovine mastitis outbreak caused byS. ruminantiumin Italy, 2022.S. ruminantiumwas isolated from 12 adult lactating ewes with diffuse nodules in the mammary parenchyma and predominantly serous and clotted milk. All outbreak isolates, along with five additional historical Italian isolates (between 2011 and 2017), were genomically characterised and then analysed in the context of all publicly availableS. ruminantiumgenomes. Antimicrobial susceptibility testing was performed to determine the MICs of 16 antibiotics. The results showed that all isolates were susceptible to all antimicrobials tested except kanamycin. Single Nucleotide Variant analysis confirmed this as a clonal outbreak across 10 sheep (≤ 15 SNVs), while the two others were colonised by more distantly related clones (≤ 53 pairwise SNVs), indicating the presence of multiple infecting lineages. The five historicalS. ruminantiumisolates were comprised of genetically-distant singletons (between 1259 and 5430 pairwise SNVs to 2022 outbreak isolates). Ovine isolates were found to be genetically distinct to bovine isolates, forming monophyletic groups. Bovine isolates were similarly made up of singleton clones in all but two isolates. Taken together, our genomic analysis using all globally available genomes is consistent with general opportunistic pathogenesis ofS. ruminantium. We encourage future genomic surveillance efforts to facilitate outbreak detection, as well as improve our understanding of this poorly-understood, multi-host, zoonotic pathogen.
Existence theory and Ulam’s stabilities for switched coupled system of implicit impulsive fractional order Langevin equations
Authors: Rizwan Rizwan , Liu Fengxia , Zheng Zhiyong , Park Choonkil , Paokanta Siriluk
Published: December 2023

In this work, a system of nonlinear, switched, coupled, implicit, impulsive Langevin equations with two Hilfer fractional derivatives is introduced. The suitable conditions and results are established to discuss existence, uniqueness, and Ulam-type stability results of the mentioned model, with the help of nonlinear functional analysis techniques and Banach’s fixed-point theorem. Furthermore, we examine our results with the help of example.
Efficient and privacy-preserving image classification using homomorphic encryption and chunk-based convolutional neural network
Authors: Jia Huixue , Cai Daomeng , Yang Jie , Qian Weidong , Wang Cong , Li Xiaoyu , Yang Shan
Published: December 2023

Image feature categorization has emerged as a crucial component in many domains, including computer vision, machine learning, and biometrics, in the dynamic environment of big data and cloud computing. It is extremely difficult to guarantee image data security, privacy, and computing efficiency while also lowering storage and transmission costs. This paper introduces a novel method for classifying image features that combines multilevel homomorphic encryption and image data partitioning in an integrated manner. We employ a novel partitioning strategy to reduce computational complexity, significantly reducing computational load and improving classification accuracy. In the quest for increased data security and privacy, we introduce a novel, fully homomorphic encryption approach specialized to partitioned images. To counter the inherent complexity of encryption, we devise a compound encryption strategy that exploits the full potential of homomorphic computation, with an explicit objective to curtail computational and storage overheads. Evidently superior to conventional methods, our methodology showcases pronounced benefits in computational efficiency, storage and transmission cost reduction, and robust security and privacy preservation. Hence, the methodology put forth in this paper presents a pioneering and efficacious resolution to the multifaceted challenges of image feature classification within the intricate milieu of cloud computing and big data.
Downscaling precipitation and temperature in the Andes: applied methods and performance—a systematic review protocol
Authors: Núñez Mejía Santiago , Villegas-Lituma Carina , Crespo Patricio , Córdova Mario , Gualán Ronald , Ochoa Johanna , Guzmán Pablo , Ballari Daniela , Chávez Alexis , Mendoza Paz Santiago , Willems Patrick , Ochoa-Sánchez Ana
Published: December 2023

Background

Global warming and climate change are threats to the world. Warmer temperatures and changes in precipitation patterns alter water availability and increase the occurrence of extreme weather events. South America and the Andes are vulnerable regions to climate change due to inequity and the uneven distribution of resources. Climate change evaluation often relies on the use of general circulation models (GCMs). However, the spatial resolution is too coarse and does not provide a realistic climate representation at a local level. This is of particular importance in mountain areas such as the Andes range, where the heterogeneous topography requires a finer spatial resolution to represent the local physical processes. To this end, statistical and/or dynamical downscaling methods are required. Several approaches and applications of downscaling procedures have been carried out in the countries of this region, with different purposes and performances. However, the main objective is to improve the representation of meteorological variables such as precipitation and temperature. A systematic review of these downscaling applications will identify the performance of the methods applied in the Andes region for the downscaling of precipitation and temperature. In addition, the meta-analysis could detect factors influencing the performance. The overall goal is to highlight promising methods in terms of fitness for use and identify knowledge gaps in the region.

Methods

The review will search and examine published and grey literature on downscaling applications of temperature and precipitation in the Andes region. Predetermined criteria for eligibility will allow the screening of the evidence. Then, the method used in each application will be coded and mapped according to the country, purpose, variable, and type of downscaling. At the same time, quantitative and qualitative data will be extracted. The performance metrics are particularly interesting for this review. A meta-analysis will be conducted for those studies with comparable metrics. A narrative synthesis, maps and heatmaps will show the results. Tables, funnel plots, and meta-regressions will present the meta-analysis. Throughout the review, a critical appraisal step will categorize the validity of the evidence.
Problematic mobile phone use and time management disposition in Chinese college students: the chain mediating role of sleep quality and cognitive flexibility
Authors: Yuan Yidan , He Xinyue , He Quanxing , Jia Yimeng , Xu Zhansheng , Li Man
Published: December 2023

Background

With the widespread adoption of smartphones, there has been a notable increase in problematic mobile phone use (PMPU), particularly prevalent among college students. Research suggests that apart from being associated with various problematic behaviors, this excessive mobile phone use might also have an impact on individual personality traits, such as time management disposition (TMD), which plays a significant role in individual motivation and psychological well-being. While previous literature has identified a negative relationship between PMPU and TMD, few studies have delved into the underlying mediating mechanism. Thus, the main aim of this study was to examine the chain mediating effect of sleep quality and cognitive flexibility on the relationship between PMPU and TMD.

Methods

A total of 921 Chinese college students completed the questionnaire. We collected basic information about the participants and assessed their PMPU, TMD, sleep quality, and cognitive flexibility using the Problematic Mobile Phone Use Scale-10, Adolescence Time Management Disposition Inventory, Pittsburgh Sleep Quality Index scale and Cognitive Flexibility Inventory.

Results

The results indicated a significant correlation among all the variables. Moreover, we noted that both sleep quality and cognitive flexibility fully mediated the association between PMPU and TMD. Additionally, a chain mediating effect involving sleep quality and flexibility in this relationship was also identified.

Conclusion

We found that sleep quality and cognitive flexibility had a series of multiple mediating effects in the pathway from PMPU to TMD, and both significantly mediated TMD. These findings indicated that impaired cognitive function and sleep quality may contribute to time management difficulties resulting from PMPU, suggesting that problematic behaviors like PMPU can impact one’s personality traits. Therefore, interventions should be enhanced to mitigate the adverse effects of PMPU.