bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding complex disease‐related mechanisms: Rational therapies for Diamond–Blackfan anaemia
Authors: Lipton Jeffrey M.
Published: March 2024

The rich history surrounding Diamond–Blackfan anaemia (DBA), originally described in 1938 as congenital hypoplastic anaemia2 reflects the evolution of paediatric haematology. In their paper, the authors1 present the results of a clinical trial using the thrombopoietin‐mimetic agent eltrombopag to treat red cell failure in DBA. A low response rate belies the importance of this work.

Commentary on: Duncan et al. Treatment of refractory/relapsed Diamond–Blackfan anaemia with eltrombopag. Br J Haematol 2024;204:2077‐2085.
Thymoquinone potentiates anti‐cancer effects of cisplatin in oral squamous cell carcinoma via targeting oxidative stress
Authors: Fath Mohsen Karami , Nasiri Kamyar , Ghasemzadeh Shabnam , Nejati Seyedeh Tabasom , Ghafari Nima , Masouleh Sahand Saeidpour , Dadgar Esmaeel , Kazemi Kimia Sadat , Esfahaniani Mahla
Published: March 2024

Recent evidence has proved that thymoquinone as a natural polyphenol has great anticancer and anti‐proliferative effects in cancer cells. In this study, we aimed to examine the effects of thymoquinone on increasing cisplatin‐induced apoptosis human oral squamous cell carcinoma cells and its underlying molecular mechanisms. SCC‐25 cancer cells treated by thymoquinone and cisplatin with different concentrations. Cell viability will determine by using MTT assay. The concentrations of reactive oxygen species (ROS) and antioxidant activities were determined using specific related kits. DNA damage, lipid, and protein oxidation were assessed. Real‐time PCR and Western blot analysis will be used to determine the expression of apoptosis‐related proteins including Bax, Bcl‐2, and caspase‐3. Combination of thymoquinone and cisplatin suppressed synergistically SCC‐25 cancer cell viability and induced apoptosis in dose‐depended manner. Cell treatment with combination of thymoquinone and cisplatin led to accumulation of ROS within cells and increase in the intracellular levels of DNA damage, protein and lipid peroxidation. In addition, the combination of thymoquinone and cisplatin modulated the mRNA and protein expression levels of apoptosis‐related proteins including Bax, Bcl‐2, and caspase‐3. Thymoquinone potentiated cisplatin anti‐cancer effect on OSCC by inducing oxidative stress in cells.
Influencing factors in surgical decision‐making: a qualitative analysis of colorectal surgeons' experiences of postoperative complications
Authors: Bisset Carly N. , Moug Susan J. , Oliphant Raymond , Dames Nicola , Parson Simon , Cleland Jennifer
Published: March 2024

Aim

When making anastomotic decisions in rectal cancer surgery, surgeons must consider the risk of anastomotic leakage, which bears implications for the patient's quality of life, cancer recurrence and, potentially, death. The aim of this study was to investigate the views of colorectal surgeons on how their individual attributes (e.g. experience, personality traits) may influence their decision‐making and experience of complications.

Method

This qualitative study used individual interviews for data collection. Purposive sampling was used to invite certified UK‐based colorectal surgeons to participate. Participants were recruited until ongoing data review indicated no new codes were generated, suggesting data sufficiency. Data were analysed thematically following Braun and Clarke's six‐step framework.

Results

Seventeen colorectal surgeons (eight female, nine male) participated. Two key themes with relevant subthemes were identified: (1) personal attributes influencing variation in decision‐making (e.g. demographics, personality) and (2) the influence of complications on decision‐making. Surgeons described variation in the management of complications based upon their personal attributes, which included factors such as gender, experience and subspeciality interests. Surgeons described the detrimental impact of anastomotic leakage on their mental and physical health. Experience of anastomotic leakage influences future decision‐making and is associated with changes in practice even when a technical error is not identified.

Conclusion

Colorectal surgeons consider anastomotic leaks to be personal ‘failures’, which has a negative impact on surgeon welfare. Better understanding of how surgeons make difficult decisions, and how surgeons respond to and learn from complications, is necessary to identify ‘personalized’ methods of supporting surgeons at all career stages, which may improve patient outcomes.
soulspace: Integrated youth mental health care in Berlin, Germany—An introduction to the program and a description of its users
Authors: Bechdolf Andreas , Hanser Sinah , Baumgardt Johanna , Brose Annette , Jäckel Dorothea , Döring Sophia , Holzner Laura , Aliakbari Navid , von Hardenberg Laura , Shmuilovich Olga , Gencaggi Dilek , Schellong Mario , Izat Yonca , Leopold Stephanie , Ituarte Begoña Petuya , Leopold Karolina
Published: March 2024

Aim

A substantial gap between young people's need for mental health care services and their actual access to such services led worldwide organizations (e.g., the WHO) to recommend the implementation of early intervention programs and youth mental health services. Some countries around the world have established structures to meet this recommendation. In this paper, we describe soulspace as the first integrated youth mental health service for young people aged between 15 and 35 years in Berlin, Germany.

Methods

We introduce soulspace as easily accessible mental health care for young people, and we characterize soulspace along the lines of the internationally established eight key principles of integrated youth mental health services (Killackey, et al., 2020, World Economic Forum). Soulspace is a cooperation between clinical outpatient units of psychiatric clinics for adolescents and young adults as well as a community‐based counselling service. It provides initial contact, counselling, diagnostics, and treatment.

Results

Our analyses of the pathways to soulspace and the characteristics of the soulspace users suggest that the low threshold is a facilitator to help finding for young people in comparison to more conventional early intervention models. That is, having transferred the early intervention center in a youth‐facing counselling service as was done in soulspace seems to have reduced the threshold to seek help for families and for young people in need for support.

Conclusions

In summary, with soulspace, an easily accessible mental health care service was established that integrates counselling and specialized psychiatric treatment if needed.
Salmonella‐driven intestinal edema in mice is characterized by tensed fibronectin fibers
Authors: Rappold Ronja , Kalogeropoulos Konstantinos , auf dem Keller Ulrich , Vogel Viola , Slack Emma
Published: March 2024

Intestinal edema is a common manifestation of numerous gastrointestinal diseases and is characterized by the accumulation of fluid in the interstitial space of the intestinal wall. Technical advances in laser capture microdissection and low‐biomass proteomics now allow us to specifically characterize the intestinal edema proteome. Using advanced proteomics, we identify peptides derived from antimicrobial factors with high signal intensity, but also highlight major contributions from the blood clotting system, extracellular matrix (ECM) and protease–protease inhibitor networks. The ECM is a complex fibrillar network of macromolecules that provides structural and mechanical support to the intestinal tissue. One abundant component of the ECM observed in Salmonella‐driven intestinal edema is the glycoprotein fibronectin, recognized for its structure–function interplay regulated by mechanical forces. Using mechanosensitive staining of fibronectin fibers reveals that they are tensed in the edema, despite the high abundance of proteases able to cleave fibronectin. In contrast, fibronectin fibers increasingly relax in other cecal tissue areas as the infection progresses. Co‐staining for fibrin(ogen) indicates the formation of a provisional matrix in the edema, similar to what is observed in response to skin injury, while collagen staining reveals a sparse and disrupted collagen fiber network. These observations plus the absence of low tensional fibronectin fibers and the additional finding of a high number of protease inhibitors in the edema proteome could indicate a critical role of stretched fibronectin fibers in maintaining tissue integrity in the severely inflamed cecum. Understanding these processes may also provide valuable functional diagnostic markers of intestinal disease progression in the future.
Importance of γ′ shearing in low‐cycle fatigue of a wrought superalloy
Authors: Babinský Tomáš , Poczklán Ladislav , Gálíková Markéta , Polák Jaroslav
Published: March 2024

The present study deals with the fatigue behavior of a wrought nickel‐based superalloy René 41. Uniaxial, fully reversed low‐cycle fatigue tests were conducted at room and elevated (800°C) temperatures under total strain control. Cyclic response was analyzed using the statistical theory of the hysteresis loop, and scanning and transmission electron microscopies were employed to study relevant damage mechanisms. At room temperature, cyclic deformation was found to localize to slip bands since the first cycle, and most slip bands were formed very early in the fatigue life. Hence, shearing of the strengthening phase, coherent γ′ precipitates, was found to be significant only in the first few cycles. At 800°C, fatigue life was affected by an environmental attack resulting in a surface oxide layer. Cyclic deformation was less localized; nevertheless, cyclic slip localization in persistent slip bands and resulting γ′ shearing contributed to cyclic softening throughout the fatigue life.
Prognostic impact of the IASLC grading system of lung adenocarcinoma: a systematic review and meta‐analysis
Authors: Hegedűs Fanni , Zombori‐Tóth Noémi , Kiss Szabolcs , Lantos Tamás , Zombori Tamás
Published: March 2024

Aims

Tumour grading is an essential part of the pathologic assessment that promotes patient management. The International Association for the Study of Lung Cancer (IASLC) proposed a grading system for non‐mucinous lung adenocarcinoma in 2020. We aimed to validate the prognostic impact of this novel grading system on overall survival (OS) and recurrence‐free survival (RFS) based on literature data.

Methods and Results

The review protocol was registered in PROSPERO (CRD42023396059). We aimed to identify randomized or non‐randomized controlled trials published after 2020 comparing different IASLC grade categories in Medline, Embase, and CENTRAL. Hazard ratios (HRs) with 95% confidence intervals (CIs) of OS and RFS were pooled and the Quality In Prognosis Studies (QUIPS) tool was used to assess the risk of bias in the included studies. Ten articles were eligible for this review. Regarding OS estimates, grade 1 lung adenocarcinomas were better than grade 3 both in univariate and multivariate analyses (HROSuni = 0.19, 95% CI: 0.05–0.66, p = 0.009; HROSmulti = 0.21, 95% CI: 0.12–0.38, p < 0.001). Regarding RFS estimates, grade 3 adenocarcinomas had a worse prognosis than grade 1 in multivariate analysis (HRRFSmulti: 0.22, 95% CI: 0.14–0.35, p < 0.001).

Conclusion

The literature data and the result of our meta‐analysis demonstrate the prognostic relevance of the IASLC grading system. This supports the inclusion of this prognostic parameter in daily routine worldwide.
Implicit and Explicit Weight Bias among Midwives: Variations Across Demographic Characteristics
Authors: Bradford Heather M. , Puhl Rebecca M. , Phillippi Julia C. , Dietrich Mary S. , Neal Jeremy L.
Published: March 2024

Introduction

Weight bias toward individuals with higher body weights is present in health care settings. However, there has been limited quantitative exploration into weight bias among perinatal care providers and its potential variations based on demographic characteristics. The aim of this study was to examine if the direction and extent of weight bias among midwives certified by the American Midwifery Certification Board (AMCB) varied across age, years since certification, body mass index (BMI), race, ethnicity, and US geographic region.

Methods

Through direct email listservs, postcard distribution, social media accounts, and professional networks, midwives were invited to complete an online survey of their implicit weight bias (using the Implicit Association Test) and their explicit weight bias using the Anti‐Fat Attitudes Questionnaire (AFA), Fat Phobia Scale (FPS), and Preference for Thin People (PTP) measure.

Results

A total of 2106 midwives who identified as Black or White and resided in one of 4 US geographic regions participated in the survey. Midwives with a lower BMI expressed higher levels of implicit (P <.01) and explicit (P ≤.01) weight bias across all 4 measures except for the AFA Fear of Fat Subscale. Implicit weight bias levels also varied by age (P <.001) and years since certification (P <.001), with lower levels among younger midwives (vs older) and those with fewer years (vs more) since certification. Only age and BMI remained significant (P <.001) after adjusting for other demographic characteristics. Lower explicit weight bias levels were found among midwives who identified as Black (vs White) on 2 measures (FPS: adjusted β = −0.07, P = .004; PTP: P = .01).

Discussion

This was the first quantitative study of how weight bias varies across demographic characteristics among a national sample of midwives. Further exploration is needed in more diverse samples. In addition, research to determine whether weight bias influences clinical decision‐making and quality of care is warranted.
Restoring long‐lasting midface volume in the Asian face with a hyaluronic acid filler: A randomized controlled multicenter study
Authors: Ren Rongxin , Xue Hongyu , Gao Zhanwei , Wang Hang , Xia Xiujuan , Qu Yan , Bromée Torun , Almegård Birgitta , Zhao Hongyi
Published: March 2024

Background

Hyaluronic acid (HA) filler treatment is a minimally‐invasive alternative to surgery to volumize the cheeks. HAVOL (Restylane® Volyme) is a flexible HA filler suited to contouring and volumizing the midface.

Methods

This randomized, evaluator‐blinded, no‐treatment controlled study evaluated effectiveness and safety of HAVOL for correction of midface volume deficit and midface contour deficiency in Chinese subjects. In total 111 subjects were randomized to HAVOL and 37 to no treatment (control). The primary endpoint was response, on the blinded evaluator‐assessed Medicis Midface Volume Scale (MMVS), at 6 months after last injection for the treatment group and 6 months after randomization for controls, where response was defined as ≥1‐point improvement from baseline on both sides of the face.

Results

HAVOL was superior to no treatment at 6 months, meeting the primary objective: 76% versus 8% MMVS responders, a difference of 68% (CI: 55.7%–79.4%, p < 0.0001). These effects were sustained in 51% at 12 months after last injection. A majority (≥96%) had improved aesthetic appearance of midface fullness at Month 1 (using the Global Aesthetic Improvement Scale [GAIS]), effects which remained in ≥80% up to 12 months. Volume change captured by 3D photography increased after 1 month to 3.6 mL (close to the total injected volume of 3.4 mL), and remained stable through 12 months. Over 97% reported satisfaction with results after treatment with HAVOL. Additionally, HAVOL was well tolerated, with no unanticipated related adverse events.

Conclusions

This study showed that HAVOL is effective and well tolerated for midface treatment in a Chinese population.
Parents' perspectives on dental team as advisors to promote HPV vaccination among Spanish adolescents
Authors: Lorenzo‐Pouso Alejandro Ismael , González‐Palanca Sergio , Palmeiro‐Fernández Gerardo , Dominguez‐Salgado Juan Carlos , Pérez‐Sayáns Mario , González‐Veiga Ernesto J. , Caponio Vito Carlo Alberto , Daley Ellen M.
Published: March 2024

Purpose

Human papillomavirus (HPV) is a prevalent sexually transmitted infection responsible for many anogenital and oropharyngeal cancers. Dental care providers have the potential to influence vaccine uptake, yet little is known about how patients perceive their role in HPV education and prevention.

Methods

Parents of adolescents aged 9 to 17 years (n = 375) were recruited from Valdeorras District Hospital (Galicia, Spain) to investigate parents' attitudes concerning the involvement of dental care providers in discussions related to HPV. A survey was distributed to the participants, and 343 (91.5%) were included in the analysis.

Results

In general, nearly half of the parents reported feeling comfortable regarding discussing HPV with their dentist. Participants described more comfort with dentists than with dental hygienists. Parents' comfort levels were influenced by various social determinants of health, including education level, marital status, geographic origin, and child vaccination status (p > 0.05).

Conclusion

Parents reported varying comfort levels when discussing HPV and its vaccine with dental professionals, displaying a preference for dentists. Dental settings have the potential to promote vaccination, but the existence of ongoing barriers needs to be addressed.
Digital cognitive behavioural therapy for insomnia reduces insomnia in nurses suffering from shift work disorder: A randomised‐controlled pilot trial
Authors: Ell Johanna , Brückner Hanna A. , Johann Anna F. , Steinmetz Lisa , Güth Lara J. , Feige Bernd , Järnefelt Heli , Vallières Annie , Frase Lukas , Domschke Katharina , Riemann Dieter , Lehr Dirk , Spiegelhalder Kai
Published: March 2024

Insomnia is a primary symptom of shift work disorder, yet it remains undertreated. This randomised‐controlled pilot trial examined the efficacy of a digital, guided cognitive behavioural therapy for insomnia adapted to shift work (SleepCare) in nurses with shift work disorder. The hypothesis was that SleepCare reduces insomnia severity compared with a waitlist control condition. A total of 46 unmedicated nurses suffering from shift work disorder with insomnia (age: 39.7 ± 12.1 years; 80.4% female) were randomised to the SleepCare group or the waitlist control group. The primary outcome measure was the Insomnia Severity Index. Other questionnaires on sleep, mental health and occupational functioning, sleep diary data and actigraphy data were analysed as secondary outcomes. Assessments were conducted before (T0), after the intervention/waitlist period (T1), and 6 months after treatment completion (T2). The SleepCare group showed a significant reduction in insomnia severity from T0 to T1 compared with the control condition (β = −4.73, SE = 1.12, p < 0.001). Significant improvements were observed in sleepiness, dysfunctional beliefs about sleep, pre‐sleep arousal, sleep effort, self‐reported sleep efficiency and sleep onset latency. No significant effect was found in actigraphy data. Depressive and anxiety symptoms, cognitive irritation and work ability improved significantly. Overall, satisfaction and engagement with the intervention was high. SleepCare improved insomnia severity, sleep, mental health and occupational functioning. This is the first randomised‐controlled trial investigating the efficacy of digital cognitive behavioural therapy for insomnia in a population suffering from shift work disorder with insomnia. Future research should further explore these effects with larger sample sizes and active control conditions.
Comparison of homologous and heterologous inactivated and mRNA vaccination programme against SARS‐CoV‐2 in dialysis patients
Authors: Yasar Emre , Yildiz Yesim , Ozturk Erensu , Gok Oguz Ebru , Coskun Yenigun Ezgi , Ozturk Ramazan , Helvaci Ozant , Ozger Hasan Selcuk , Keles Meryem , Karacin Cengiz , Ugras Dikmen Asiye , Caglar Kayhan , Duranay Murat , Ayli Mehmet Deniz , Dizbay Murat , Erten Yasemin , Guz Galip , Derici Ulver
Published: March 2024

Aim

To evaluate the vaccine response and the effect of the booster dose on COVID‐19 positivity in haemodialysis (HD) and peritoneal dialysis (PD) patients who received and did not receive BNT162b2 as a booster dose after two doses of CoronaVac.

Methods

The study included 80 PD and 163 HD patients, who had been administered two doses of the CoronaVac. Antibody levels were measured on Days 42 and 90 after the first dose. Measurements were repeated on Day 181 after the first dose in the patients that received two vaccine doses and on Day 28 after the third dose in those that also received the booster dose. Antibody levels below 50 AU/mL were considered negative.

Results

The seropositivity rate was similar in the HD and PD group on Days 42 and 90 (p = 0.212 and 0.720). All patients were seropositive in the booster group. The antibody level was lower in the patients that received CoronaVac as the booster compared to those administered BNT162b2 in HD and PD groups (p < 0.001 and 0.002). COVID‐19 positivity was detected in 11 patients (7 = had not received the booster dose, 4 = had received third dose of CoronaVac). The multivariate analysis revealed that as age increased, COVID‐19 positivity also increased (OR: 1.080, 95% CI: 1.017 – 1.146, p = 0.012), while booster dose administration decreased this positivity (OR: 0.113, 95% CI: 0.028 – 0.457, p = 0.002).

Conclusion

Our results may indicate the need for additional vaccination doses in patients with HD and PD. Our findings indicate a higher antibody response in dialysis patients with heterologous BNT162b2 as a booster dose after two doses of CoronaVac compared to homologous CoronaVac.

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Association of Handgrip Strength with Hip Fracture and Falls in Community‐dwelling Middle‐aged and Older Adults: A 4‐Year Longitudinal Study
Authors: Guo Tianting , Zhang Fei , Xiong Lijiao , Huang Zhihua , Zhang Xiaoan , Wan Junming , Mo Jianwen
Published: March 2024

Objective

Hip fracture and falls are significant health concerns. Handgrip strength (HGS) is closely associated with overall muscle strength and physical health. However, the longitudinal relationship between HGS and the risk of hip fractures and falls remains unclear, particularly regarding gender differences. This longitudinal study aimed to investigate the association between HGS and the risk of hip fracture and falls in individuals aged 45 years and above, considering gender‐specific differences over a 4‐year period.

Methods

This study included 10,092 participants (4471 men and 5621 women) aged 45 years and above from the China Health and Retirement Longitudinal Study (CHARLS). Incidents of hip fractures and falls were recorded during a 4‐year follow‐up, along with various demographic and clinical factors. Participants were categorized into five groups based on their HGS quintiles. Logistic regression models were employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationship between HGS and hip fracture/fall risk.

Results

During the 4‐year follow‐up period, 223 cases of hip fracture (2.2%) and 1831 cases of falls (18.1%) were documented. Notably, higher HGS demonstrated a strong inverse association with the risk of hip fracture in both males and females (p < 0.05). In comparison to the lowest HGS quintile, the adjusted odds ratios (ORs) for hip fracture were 0.46 (0.27–0.78) for the total population, 0.4 (0.19–0.81) for males and 0.48 (0.23–0.98) for females in the highest HGS quintile. Furthermore, a profound and statistically significant negative correlation between HGS and falls was detected (p < 0.05). The adjusted ORs for falls in the highest HGS quintile, compared to the lowest quintile, were 0.62 (0.51–0.76) in the overall population, 0.59 (0.44–0.78) in males, and 0.78 (0.62–0.99) in females.

Conclusion

Our findings highlight the significant inverse association between HGS and the risk of hip fracture and falls in both males and females aged 45 years and above. Assessing handgrip strength may serve as a valuable tool for predicting fracture and fall risk.
Metal‐semiconductor heterojunction accelerates the plasmonically powered photoregeneration of biological cofactors
Authors: Deepak Namitha , Jain Vanshika , Pillai Pramod P.
Published: March 2024

Photocatalysis with plasmonic nanoparticles (NPs) is emerging as an attractive strategy to make and break chemical bonds. However, the fast relaxation dynamics of the photoexcited charge carriers in plasmonic NPs often result in poor yields. The separation and extraction of photoexcited hot‐charge carriers should be faster than the thermalization process to overcome the limitation of poor yield. This demands the integration of rationally chosen materials to construct hybrid plasmonic photocatalysts. In this work, the enhanced photocatalytic activity of gold nanoparticle‐titanium dioxide metal‐semiconductor heterostructure (Au‐TiO2) is used for the efficient regeneration of nicotinamide (NADH) cofactors. The modification of plasmonic AuNPs with n‐type TiO2 semiconductor enhanced the charge separation process, because of the Schottky barrier formed at the Au–TiO2 heterojunction. This led to a 12‐fold increment in the photocatalytic activity of plasmonic AuNP in regenerating NADH cofactor. Detailed mechanistic studies revealed that Au‐TiO2 hybrid photocatalyst followed a less‐explored light‐independent pathway, in comparison to the conventional light‐dependent path followed by sole AuNP photocatalyst. NADH regeneration yield reached ~70% in the light‐independent pathway, under optimized conditions. Thus, our study emphasizes the rational choice of components in hybrid nanostructures in dictating the photocatalytic activity and the underlying reaction mechanism in plasmon‐powered chemical transformations.
Promotion of Physical Activity by Québec Primary Care Physicians: What Has Changed in the Last Decade?
Authors: Laberge Suzanne , Gosselin Véronique , Lestage Kim , Chagnon Miguel , Guimond Claude
Published: March 2024

Objective: This study aimed to assess the changes in the frequency of physical activity (PA) counseling and in the predictors of primary care PA promotion in Québec primary care physicians (PCPs) between 2010 and 2020. Methods: In 2010, we conducted a survey among Québec PCPs. Questions included: frequency of promoting PA to patients, perceived barriers, needs to improve PA promotion practice, frequency of PCPs’ PA practice, and sociodemographic information. In 2020, we took over the 2010 questionnaire to document the evolution of the PA promotion practice. Results: The proportion of PCPs discussing PA with their patients significantly increased (P < .05) in 2020 for the following health conditions: depression, low back pain, chronic obstructive pulmonary disease, and cancer; it declined (P < .05) for overweight patients, those with metabolic syndrome, and in primary prevention. Collaboration with PA professionals was the major need identified, and it increased in 2020. PCPs’ own practice of PA was a predictor of PA promotion in 2010 (odds ratio = 6.679; P < .001) and in 2020 (odds ratio  = 6.679; P < .001). In both 2010 and in 2020, older or more experienced PCPs were more likely to discuss PA with their patients without diagnosed diseases than younger ones or those with less experience. Conclusions: Over the last 10 years, there has been a significant increase in PCPs promoting PA in Québec; however, it has been mainly oriented toward secondary prevention. It is concerning that PA counseling in primary prevention has declined, notably among younger PCPs. The stronger claim for closer collaboration with kinesiologists suggests that PCPs are in favor of an interprofessional strategy, namely collaboration with PA specialists.
CKLF instigates a “cold” microenvironment to promote MYCN-mediated tumor aggressiveness
Authors: Qin Xiaodan , Lam Andrew , Zhang Xu , Sengupta Satyaki , Iorgulescu J. Bryan , Ni Hongru , Das Sanjukta , Rager Madison , Zhou Zhenwei , Zuo Tao , Meara Grace K. , Floru Alexander E. , Kemet Chinyere , Veerapaneni Divya , Kashy Daniel , Lin Liang , Lloyd Kenneth , Kwok Lauren , Smith Kaylee S. , Nagaraju Raghavendar T. , Meijers Rob , Ceol Craig , Liu Ching-Ti , Alexandrescu Sanda , Wu Catherine J. , Keskin Derin B. , George Rani E. , Feng Hui
Published: March 2024

Solid tumors, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. We found that chemokine-like factor (
CKLF
) is highly expressed by various solid tumor cells and transcriptionally up-regulated by MYCN. Using the MYCN-driven high-risk neuroblastoma as a model system, we demonstrated that as early as the premalignant stage, tumor cells secrete CKLF to attract CCR4-expressing CD4
+
cells, inducing immunosuppression and tumor aggression. Genetic depletion of CD4
+
T regulatory cells abolishes the immunorestrictive and protumorigenic effects of CKLF. Our work supports that disrupting CKLF-mediated cross-talk between tumor and CD4
+
suppressor cells represents a promising immunotherapeutic approach to battling MYCN-driven tumors.
Tracing the dynamics of superconducting order via transient terahertz third-harmonic generation
Authors: Kim Min-Jae , Kovalev Sergey , Udina Mattia , Haenel Rafael , Kim Gideok , Puviani Matteo , Cristiani Georg , Ilyakov Igor , de Oliveira Thales V. A. G. , Ponomaryov Alexey , Deinert Jan-Christoph , Logvenov Gennady , Keimer Bernhard , Manske Dirk , Benfatto Lara , Kaiser Stefan
Published: March 2024

Ultrafast optical control of quantum systems is an emerging field of physics. In particular, the possibility of light-driven superconductivity has attracted much of attention. To identify nonequilibrium superconductivity, it is necessary to measure fingerprints of superconductivity on ultrafast timescales. Recently, nonlinear THz third-harmonic generation (THG) was shown to directly probe the collective degrees of freedoms of the superconducting condensate, including the Higgs mode. Here, we extend this idea to light-driven nonequilibrium states in superconducting La2-xSrxCuO4, establishing an optical pump–THz–THG drive protocol to access the transient superconducting order-parameter quench and recovering on few-picosecond timescales. We show in particular the ability of two-dimensional TH spectroscopy to disentangle the effects of optically excited quasiparticles from the pure order-parameter dynamics, which are unavoidably mixed in the pump-driven linear THz response. Benchmarking the gap dynamics to existing experiments shows the ability of driven THG spectroscopy to overcome these limitations in ordinary pump-probe protocols.
RORγt up-regulates RAG gene expression in DP thymocytes to expand the
Tcra
repertoire
Authors: Naik Abani Kanta , Dauphars Danielle J. , Corbett Elizabeth , Simpson Lunden , Schatz David G. , Krangel Michael S.
Published: March 2024

Recombination activating gene (RAG) expression increases as thymocytes transition from the CD4
−
CD8
−
double-negative (DN) to the CD4
+
CD8
+
double-positive (DP) stage, but the physiological importance and mechanism of transcriptional up-regulation are unknown. Here, we show that a DP-specific component of the recombination activating genes antisilencer (DPASE) provokes elevated RAG expression in DP thymocytes. Mouse DP thymocytes lacking the DPASE display RAG expression equivalent to that in DN thymocytes, but this supports only a partial
Tcra
repertoire due to inefficient secondary Vα-Jα rearrangement. These data indicate that RAG up-regulation is required for a replete
Tcra
repertoire and that RAG expression is fine-tuned during lymphocyte development to meet the requirements of distinct antigen receptor loci. We further show that transcription factor RORγt directs RAG up-regulation in DP thymocytes by binding to the DPASE and that RORγt influences the
Tcra
repertoire by binding to the
Tcra
enhancer. These data, together with prior work showing RORγt to control
Tcra
rearrangement by regulating DP thymocyte proliferation and survival, reveal RORγt to orchestrate multiple pathways that support formation of the
Tcra
repertoire.
Anti-interleukin-6 receptor antibody for the treatment of remitting seronegative symmetrical synovitis with pitting oedema: a new outlook?
Authors: Noversa de Sousa Rita , Marques Rocha Diana , Nair Simões Marisa , Rosário Cristina
Published: March 2024

We present the case of an elderly man with a small-joint polyarthritis, accompanied by pitting oedema, involving hands and feet, raising clinical suspicion of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). Treatment with corticosteroids was initiated with significant improvement, but unacceptable iatrogeny ensued, and tapering was not possible without disease flare-up. A trial of tocilizumab allowed disease activity control, slow weaning of corticosteroids and, ultimately, its suspension. RS3PE is a rare rheumatological entity, initially thought to be a variant of rheumatoid arthritis (RA), with shared traits with polymyalgia rheumatica (PMR), and other seronegative spondyloarthropathies, thereby implying a shared pathophysiological background. Elevated levels of interleukin 6 (IL-6) are found in patients with RA, have shown to mirror disease activity in PMR and have also been described in the serum and synovial fluid of patients with RS3PE. Tocilizumab, an anti-IL-6 receptor antibody, shows auspicious results in several other rare rheumatic diseases other than RA.
Non-vertebralMycobacterium aviumcomplex osteomyelitis in an immunocompetent patient
Authors: McAllister Rebecca , Magee Anthony , Kelly Sean
Published: March 2024

Mycobacterium aviumcomplex (MAC) is a ubiquitous soil pathogen that is an uncommon cause of diseases in immunocompetent patients. In this case, we describe the presentation of an otherwise healthy man in his 50s presenting with months of malaise and severe hip pain, with aspiration initially yielding no bacteria and presumed fastidious infection. He was treated with irrigation and debridement, surgical stabilisation of the femoral neck and conventional broad-spectrum antibiotics with final cultures diagnostic of MAC osteomyelitis. This case serves to demonstrate the importance of clinical suspicion and appropriate workup of this unusual case of MAC hip osteomyelitis in an otherwise immunocompetent patient.
Presentation and multidisciplinary management of a unique case of lower limb dysmelia resulting from amniotic band syndrome
Authors: Radcliffe Katherine , Gohil Kajal , Bedford James D
Published: March 2024

A neonate was born with a unique congenital lower limb dysmelia due to an abnormal presentation of amniotic band syndrome. An anomalous soft tissue tether from the plantar surface of the right foot to the right buttock caused extreme knee flexion, tibial rotation and malformation of the developing foot. This complex malformation required a multidisciplinary team (MDT) approach to decide between reconstruction and amputation. The band of tissue was released operatively at 73 days postdelivery, improving knee extension, and the tissue was banked on the thigh as a tube pedicle for future reconstruction. The patient underwent rehabilitation, which has been shown to be vital for synovial joint formation. At 18 months old, the decision was made to proceed with through-knee amputation and a prosthesis. The literature discussed shows the importance of an MDT approach in complex lower limb cases to give the best functional outcome for the patient.
Lemierre syndrome with pulmonary empyema caused byPrevotella intermedia
Authors: Simsek Bahadir , Zhang Renee , Morton Christopher , Villanueva Merceditas S
Published: March 2024

Lemierre syndrome is a rare disease that is most often caused byFusobacterium necrophorum. We present a case caused byPrevotella intermediain a young, healthy man, complicated by multiple cavitary lung lesions, loculated pleural effusions requiring chest tube placement and trapezius abscess. Our case highlights (a)P. intermediaas a rare cause of Lemierre syndrome and (b) clinical response to appropriate antimicrobial therapy may be protracted.
Aorto-atrial tunnel arising from sinus of Valsalva aneurysm in a young female
Authors: Chigullapalli Sridevi , Malani Susheel Kumar , Nalawade Digvijay , Musuku Manisha Reddy
Published: March 2024

A young female patient presented with complaints of breathlessness and palpitations since 2 years. On clinical examination, there was a loud continuous murmur at the right sternal border.

Transthoracic echocardiography and colour Doppler showed a tunnel-like structure originating from the aneurysmal right coronary sinus and opening into the right atrium with left to right shunt. Coronary angiography revealed a large tunnel beginning in right coronary sinus and terminating in the right atrium and right coronary artery (RCA) was seen originating from the tunnel. Cardiac catheterisation revealed normal pulmonary artery pressure. CT and 3D-reconstructed images delineated the extracardiac course of the tunnel.

Various treatment modalities including percutaneous transcatheter approach and surgical treatment were taken into consideration, but because of the close proximity of RCA from the tunnel opening, surgical closure was preferred.
Role of twinnings in scaling up innovative solutions across Europe
Authors: Campos Cláudia , Kappelhof Robbin , Carrilho Joana , Midão Luis , Henriques Diogo , Costa Elísio
Published: March 2024

Introduction

Twinnings are cross-border knowledge exchange activities where two or more organisations learn from each other’s experiences and are often used as a scaling up mechanism.

Objectives

This paper discusses the importance of twinning activities in scaling up by promoting community building, knowledge sharing and innovation transfer among stakeholders in European countries. It explores the role of twinnings in the scaling up model of the European Innovation Partnership on Active and Healthy Ageing) and the Innovation Networks for Scaling Active and Healthy Ageing (IN-4-AHA) project.

Methods

The study employed a qualitative approach, drawing insights from various sources, including the Scale AHA study (2017), the IN-4-AHA’s scaling up model and twinning reports.

Results

The findings reveal that twinning activities provide stakeholders with a unique opportunity to learn from the know-how of other like-minded partners, improve the quality of their work and iterate on their innovations. They also highlight that twinnings are particularly relevant for some stages in the scaling up process, such as in the assessment of a network of potential partners and during the evaluation of the environment, the innovation could potentially be transferred to.

Conclusion

Twinnings are highly regarded as community-building and knowledge-sharing activities with clear advantages for companies and other stakeholder groups. Including twinning activities in the scaling up model has proven benefits for companies and projects that have a strong need for community building and innovation transfer.
STENOSIS: Long-term single versus dual antiplatelet therapy in patients with ischaemic stroke due to intracranial atherosclerotic disease – a randomised trial
Authors: Bhatia Rohit , Padma Srivastava MV , Sarkar Risha , Fatima Saman , Longkumer Imnameren , Garg Ajay , Gupta Pooja , Pandian Jeyaraj Durai , Khurana Dheeraj , Sylaja PN , Jain Shweta , Arora Deepti , Dhasan Aneesh , Sharma Meenakshi
Published: March 2024

Rationale

Intracranial atherosclerotic disease (ICAD) is a pathological process that causes progressive stenosis and cerebral hypoperfusion, leading to stroke occurrence and recurrence around the world. The exact duration of dual antiplatelet therapy (DAPT) for ICAD is unclear in view of long-term risk of bleeding complications.

Aim

The current study aims to study the efficacy and safety of long-term DAPT (up to 12 months) in patients with ICAD.

Sample size

Using 80% power and an alpha error of 5 %, presuming a 10%–15% drop-out rate, a total of 2200 patients will be recruited for the study.

Methodology

This is a prospective, randomised, double-blind, placebo controlled trial.

Study outcomes

The primary outcomes include recurrent ischaemic stroke (IS) or transient ischaemic attack and any intracranial haemorrhage (ICH), major or minor systemic bleeding at the end of 12 months. Secondary outcomes include composite of any stroke, myocardial infarction or death at the end of 12 months. The safety outcomes include any ICH, major or minor bleeding as defined using GUSTO (Global Use of Streptokinase and tPA for occluded Coronary Arteries) classification at the end of 12 months and 1 month after completion of the drug treatment phase.

Discussion

The study will provide level I evidence on the duration of DAPT among patients with IS due to ICAD of more than or equal to 50%.
Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy: a population-based cohort study
Authors: Best Catherine Susan , Matheson Catriona , Robertson James , Ritchie Trina , Cowden Fiona , Dumbrell Josh , Duncan Clare , Kessavalou Karthigayan , Woolston Caroline , Schofield Joe
Published: March 2024

Objective

To investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone.

Design

Population-based cohort study.

Setting

Scotland, UK.

Participants

Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above.

Main outcome measures

All-cause mortality, drug-related deaths and non-drug related deaths.

Secondary outcome

ORT continuous treatment duration.

Analysis

Cox regression with time-varying covariates.

Results

During follow-up, 5776 of 46 899 participants died: 1398 while on coprescription and 4378 while on ORT only. The mortality per 100 person years was 3.11 during coprescription and 2.34 on ORT only. The adjusted HR for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted HR for drug-related death was 1.14 (95% CI, 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI, 1.09 to 1.30).

Conclusion

Coprescription of BZDs in ORT was associated with an increased risk of all-cause mortality, although with a small effect size than the international literature. Coprescribing was also associated with longer retention in treatment. Risk from BZD coprescription needs to be balanced against the risk from illicit BZDs and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide a clear clinical direction.

Trial registration number

NCT04622995.
Subphenotypes of self-reported symptoms and outcomes in long COVID: a prospective cohort study with latent class analysis
Authors: Kitsios Georgios D , Blacka Shawna , Jacobs Jana J , Mirza Taaha , Naqvi Asma , Gentry Heather , Murray Cathy , Wang Xiaohong , Golubykh Konstantin , Qurashi Hafiz , Dodia Akash , Risbano Michael , Benigno Michael , Emir Birol , Weinstein Edward , Bramson Candace , Jiang Lili , Dai Feng , Szigethy Eva , Mellors John W , Methe Barbara , Sciurba Frank C , Nouraie Seyed Mehdi , Morris Alison
Published: March 2024

Objective

To characterise subphenotypes of self-reported symptoms and outcomes (SRSOs) in postacute sequelae of COVID-19 (PASC).

Design

Prospective, observational cohort study of subjects with PASC.

Setting

Academic tertiary centre from five clinical referral sources.

Participants

Adults with COVID-19 ≥20 days before enrolment and presence of any new self-reported symptoms following COVID-19.

Exposures

We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardised assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via quantitative PCR.

Outcomes measures

Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA) and relationship with viral load.

Results

We analysed baseline data for 214 individuals with a study visit at a median of 197.5 days after COVID-19 diagnosis. Participants reported ever having a median of 9/16 symptoms (IQR 6–11) after acute COVID-19, with muscle-aches, dyspnoea and headache being the most common. Fatigue, cognitive impairment and dyspnoea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3 (1–6)) than those ever experienced (p<0.001). Unsupervised LCA of symptoms revealed three clinically active PASC subphenotypes: a high burden constitutional symptoms (21.9%), a persistent loss/change of smell and taste (20.6%) and a minimal residual symptoms subphenotype (57.5%). Subphenotype assignments were strongly associated with self-assessments of global health, recovery and PASC impact on employment (p<0.001) as well as referral source for enrolment. Viral persistence (5.6% saliva and 1% stool samples positive) did not explain SRSOs or subphenotypes.

Conclusions

We identified three distinct PASC subphenotypes. We highlight that although most symptoms progressively resolve, specific PASC subpopulations are impacted by either high burden of constitutional symptoms or persistent olfactory/gustatory dysfunction, requiring prospective identification and targeted preventive or therapeutic interventions.
IMPROVE study protocol, investigating post-stroke local muscle vibrations to promote cerebral plasticity and functional recovery: a single-blind randomised controlled trial
Authors: Julliand Sophie , Papaxanthis Charalambos , Delphin Corentin , Mock Anne , Raumel Marc-Antoine , Gueugnon Mathieu , Ornetti Paul , Laroche Davy
Published: March 2024

Introduction

Spasticity is a frequent disabling consequence following a stroke. Local muscle vibrations (LMVs) have been proposed as a treatment to address this problem. However, little is known about their clinical and neurophysiological impacts when used repeatedly during the subacute phase post-stroke. This project aims to evaluate the effects of a 6-week LMV protocol on the paretic limb on spasticity development in a post-stroke subacute population.

Methods and analysis

This is an interventional, controlled, randomised, single-blind (patient) trial. 100 participants over 18 years old will be recruited, within 6 weeks following a first stroke with hemiparesis or hemiplegia. All participants will receive a conventional rehabilitation programme, plus 18 sessions of LMV (ie, continuously for 30 min) on relaxed wrist and elbow flexors: either (1) at 80 Hz for the interventional group or (2) at 40 Hz plus a foam band between the skin and the device for the control group.

Participants will be evaluated at baseline, at 3 weeks and 6 weeks, and at 6 months after the end of the intervention. Spasticity will be measured by the modified Ashworth scale and with an isokinetic dynamometer. Sensorimotor function will be assessed with the Fugl-Meyer assessment of the upper extremity. Corticospinal and spinal excitabilities will be measured each time.

Ethics and dissemination

This study was recorded in a clinical trial and obtained approval from the institutional review board (Comité de protection des personnes Ile de France IV, 2021-A03219-32). All participants will be required to provide informed consent. The results of this trial will be published in peer-reviewed journals to disseminate information to clinicians and impact their practice for an improved patient’s care.

Trial registration number

Clinical Trial:NCT05315726

Dataset

EUDRAct