bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bioinspired Robotic Finger for Multimodal Tactile Sensing Powered by Fiber Optic Sensors
Authors: Mao Baijin , Zhou Kunyu , Xiang Yuyaocen , Zhang Yuzhu , Yuan Qiangjing , Hao Hongwei , Chen Yaozhen , Liu Houde , Wang Xueqian , Wang Xiaohao , Qu Juntian
Published: June 2024

The rapid advancement of soft robotic technology emphasizes the growing importance of tactile perception. Soft grippers, equipped with tactile sensing, can gather interactive information crucial for safe human–robot interaction, wearable devices, and dexterous manipulation. However, most soft grippers with tactile sensing abilities have limited modes of tactile perception, restricting their dexterity and safety. In addition, existing tactile systems are often complicated, leading to unstable perception signals. Inspired by various organisms, a novel multimodal tactile‐sensing soft robotic finger is proposed. This finger, based on a modified fin ray structure, integrates a distributed fiber optic sensing system as part of its tactile sensory neural system. It replicates human finger capabilities, discerning contact forces as low as 0.01 N with exceptional sensitivity (106.96 mN nm−1). Through training neural networks models, the finger achieves an accuracy exceeding 96% in recognizing roughness, material stiffness, and finger pad position. Assembled into two‐finger parallel gripper, it demonstrates precise manipulation capabilities for fragile items like strawberries and potato chips. Moreover, through synergistic interplay of multimodal tactile sensing, this finger can successfully grasp an underwater transparent sphere, mitigating limitations of visual perception. The developed soft finger holds promise in various scenarios including hazardous environment detection and specialized grasping tasks.
Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives
Authors: Liu Zhuo‐Ting , Liu Ming‐Han , Xiong Yan , Wang Yan‐Jiang , Bu Xian‐Le
Published: June 2024

Alzheimer's disease (AD) is a neurodegenerative disease that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between the brain and bone, but the interaction between bone and brain in AD remains unclear. In this review, we summarize human studies of the association between bone and brain and provide an overview of their interactions and the underlying mechanisms in AD. We review the effects of AD on bone from the aspects of AD pathogenic proteins, AD risk genes, neurohormones, neuropeptides, neurotransmitters, brain‐derived extracellular vesicles (EVs), and the autonomic nervous system. Correspondingly, we elucidate the underlying mechanisms of the involvement of bone in the pathogenesis of AD, including bone‐derived hormones, bone marrow‐derived cells, bone‐derived EVs, and inflammation. On the basis of the crosstalk between bone and the brain, we propose potential strategies for the management of AD with the hope of offering novel perspectives on its prevention and treatment.

Highlights

The pathogenesis of AD, along with its consequent changes in the brain, may involve disturbing bone homeostasis.

Degenerative bone disorders may influence the progression of AD through a series of pathophysiological mechanisms.

Therefore, relevant bone intervention strategies may be beneficial for the comprehensive management of AD.
Molecular detection and association of 12.1 kb deletion within the high mobility AT‐hook 2 gene in the Netherlands dwarf rabbit (Oryctolagus Cuniculus)
Authors: Nguyen Tai Duc , Van Dang Lam , Tran Phuong Nhu Nguyen , Van Nguyen Dai , Bui Anh Phu Nam
Published: June 2024

Rabbits are mainly bred for human consumption and medical research. However, it has been recently showed that several rabbit breeds are also kept as pets for human leisure. The Netherlands dwarf rabbit is currently in the immense interest of many Vietnamese customers due to its personality and miniature stature. However, 12.1 kb deletion from position 44,709,089 to 44,721,236 bp in the high mobility AT‐hook 2 (HMGA2) gene on chromosome 4 was identified as the structural variant causing dwarfism and altered craniofacial development in this breed. It has been documented that HMGA2 plays an important role in regulating growth and individuals with genotype HMGA2 del/del are fatal several days after birth. Despite the economically high value of the Netherlands dwarf rabbit, there has been no study on the genetic survey of lethal alleles in this breed in Vietnam. The aim of this study is to develop a fast and reliable method to screen the frequency of lethal alleles of HMGA2 in the South of Vietnam. Rabbit saliva was collected, and DNA extraction was followed. Multiplex polymerase chain reaction (PCR) with three primers was optimized and performed to detect the presence of 12.1 kb deletion within the HMGA2 sequence. Our data showed that the 12.1 kb deletion in the Netherlands dwarf rabbit population was detected by our optimized multiplex PCR. In 100 rabbit animals, 34 and 16 individuals were homozygous wild type (+/+) and homozygous mutant (del/del), respectively, while 50 rabbits were heterozygous. The frequency of HMGA2 lethal allele carrier was 66% (66/100 individuals). Our results indicated that we successfully developed a fast, accurate multiplex PCR to detect carrier individuals. Verification of the genotypes was followed by sequencing. We recommend implementing our multiplex PCR procedure in genetic selection for carrier and homozygous wild‐type animals in the mating scheme to prevent the lethality of the rabbit offspring. Additionally, awareness should be raised among rabbit breeders to monitor the genetic makeup of the Netherlands dwarf rabbit populations. However, due to the limitation of the sample size, more samples should be taken in future studies to obtain the genetic frequency of the HMGA2 lethal allele more accurately.
Online psychological support in the COVID‐19 era: Social representations, trust and perceived effectiveness from the perspectives of clients and professionals
Authors: Colì Elisa , Gavrila Loredana , Cozzo Dacia , Falcone Rino
Published: June 2024

Background

This study examined the topic of online psychological counselling, focusing on the perspectives of both clients and professionals. In light of the widespread adoption of computer‐mediated psychological support during the COVID‐19 pandemic, the research analysed how it has taken shape in the collective consciousness, the role of trust, and perceived effectiveness.

Method

The sample consisted of 133 professionals (M = 46) and 716 patients (M = 33), recruited through non‐probabilistic snowball sampling. Data, collected through two ad hoc questionnaires, were analysed using the EVOC 2005 software (for social representations) and SPSS (for quantitative data).

Results

Overall, regarding the social representation of online psychological support, in the central core of the therapists' representation there seems to be a structured idea of the emotional distance that online therapy inevitably brings with it. In the core of the patients' representation, the idea of online support has been structured as a form of assistance that has shown its full usefulness during the pandemic.

Quantitative data reveal a perceived efficacy of online psychological support comparable to in‐person therapy. Efficacy is enhanced by an already‐established trust relationship. The adoption of the online mode seems to have favoured the deployment of new resources by therapists and patients, attesting to an adaptation to this new way of conducting therapy. The online mode, in particular, will continue to be chosen by both, along with face‐to‐face meetings, as a mode of psychological support post‐pandemic.

Conclusion

Based on these findings, this study holds strong potential for practical application in the field of remote therapy.
A comparison of patient ratings and staff ratings of disability using the World Health Organisation Disability Assessment Schedule in individuals with psychotic spectrum disorders who are forensic psychiatric inpatients
Authors: Källman Malin V. , Hedlund‐Lindberg Mathilde , Kristiansson Marianne , Johansson Anette G. M.
Published: June 2024

Background

Psychosocial rehabilitation in forensic psychiatric services requires sound measurement of patient and staff perceptions of psychosocial function. The recommended World Health Organisation Disability Assessment Schedule 2.0 (WHODAS), designed for this, has not been examined with offender patients.

Aims

To examine patient and staff WHODAS ratings of secure hospital inpatients with psychosis, any differences between them and explore associations with other clinical factors.

Methods

Seventy‐three patients self‐rated on the WHODAS after 3 months as inpatients. An occupational therapist interviewed the patient's primary nurse and care team at about the same time (staff ratings). Scores were calculated according to the WHODAS manual. WHODAS scores and interview‐rated symptom severity, cognitive measures, daily antipsychotic dose and duration of care were compared.

Results

Patient ratings indicated less disability than staff ratings for total score and for the domains of understanding and communicating, getting along and life activities. Self‐care and participation ratings were similar. Patients were more likely to rate themselves as disabled in getting around (mobility). Only one‐fifth of patient‐ and staff‐ ratings (16, 22%) were similar, while for nearly a third of the patients (23, 32%) self‐ratings were higher than staff ratings. More severe positive symptoms were associated with higher self‐rated WHODAS disability after accounting for treatment duration, negative symptoms, cognitive score and antipsychotic dose. No variable accounted for the staff/patient differences in ratings.

Conclusion

Our mean WHODAS score findings echoed those in other patient samples—of patient underestimation of disability, linked to severity of symptoms. In this study using the WHODAS for the first time in a forensic mental health secure inpatient service, however, we found that, by comparing individuals, half of the patients reported equivalent or greater disability than did staff. Future research should focus on elucidating from patients what contributes to their self‐ratings. Understanding their thought processes in rating may enhance rehabilitation planning.
A qualitative approach to understanding the drivers of unequal receipt of definitive therapy for Black men with prostate cancer in Massachusetts
Authors: Labban Muhieddine , Stone Benjamin V. , Steele Grant L. , Salinas Kevin E. , Agudile Emeka , Katz Mark H. , Rihan‐Porter Nancy , Reich Amanda J. , Cole Alexander P. , Landers Stewart , Trinh Quoc‐Dien
Published: June 2024

Background

Despite mandated insurance coverage since 2006 and robust health infrastructure in urban settings with high concentrations of minority patients, race‐based disparities in prostate cancer (PCa) treatment persist in Massachusetts. In this qualitative study, the authors sought to identify factors driving inequities in PCa treatment in Massachusetts.

Methods

Four hospitals offering PCa treatment in Massachusetts were selected using a case‐mix approach. Purposive sampling was used to conduct semistructured interviews with hospital stakeholders. Additional interviews were conducted with representatives from grassroots organizations providing PCa education. Two study staff coded the interviews to identify major themes and recurrent patterns.

Results

Of the 35 informants invited, 25 participated in the study. Although national disparities in PCa outcomes were readily discussed, one half of the informants were unaware that PCa disparities existed in Massachusetts. Informants and grassroots organization representatives acknowledged that patients with PCa are willing to face transportation barriers to receive treatment from trusted and accommodating institutions. Except for chief equity officers, most health care providers lacked knowledge on accessing or using metrics regarding racial disparities in cancer outcomes. Although community outreach was recognized as a potential strategy to reduce treatment disparities and engender trust, informants were often unable to provide a clear implementation plan.

Conclusions

This statewide qualitative study builds on existing quantitative data on the nature and extent of disparities. It highlights knowledge gaps in recognizing and addressing racial disparities in PCa treatment in Massachusetts. Improved provider awareness, the use of disparity metrics, and strategic community engagement may ensure equitable access to PCa treatment.

Plain Language Summary

Despite mandated insurance and urban health care access, racial disparities in prostate cancer treatment persist in Massachusetts.

This qualitative study revealed that, although national disparities were acknowledged, awareness about local disparities are lacking.

Stakeholders highlighted the importance of ancillary services, including translators, rideshares, and navigators, in the delivery of care.

In addition, whereas hospital stakeholders were aware of collected equity outcomes, they were unsure whether and who is monitoring equity metrics.

Furthermore, stakeholders agreed that community outreach showed promise in ensuring equitable access to prostate cancer treatment.

Nevertheless, most interviewed stakeholders lacked clear implementation plans.
Clinical utility of comprehensive liquid molecular profiling in patients with advanced endometrial cancer
Authors: Blanc‐Durand Félix , Camilleri Geraldine M. , Bayle Arnaud , Aldea Mihaela , Vasseur Damien , Ouali Kaissa , Michels Judith , Pautier Patricia , Nicotra Claudio , Ngo‐Camus Maud , Lacroix Ludovic , Rouleau Etienne , Ponce‐Aix Santiago , Italiano Antoine , Leary Alexandra
Published: June 2024

Background

Molecular characterization has significantly improved the management of advanced endometrial cancer (EC). It distinguishes four molecular subclasses associated with prognosis and personalized therapeutic strategies. This study assesses the clinical utility of cell‐free DNA (cfDNA) profiling in EC to identify targetable alterations.

Methods

Women with metastatic or recurrent EC were prospectively recruited within the framework of the STING trial (NCT04932525), during which cfDNA was analyzed. Genomic alterations were identified with the FoundationOne CDx assay. Each molecular report underwent review by a molecular tumor board. Alterations were categorized via the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT).

Results

A total of 61 patients were enrolled. The median age was 66.9 years, with 43% presenting frontline metastatic disease. All histologic subgroups were represented. Notably, 89% of patients yielded informative cfDNA analysis. Six tumors were classified with deficient mismatch repair/microsatellite instability (11%) and 37 as TP53 gene mutant (67%), and 12 had nonspecific molecular profiles (22%). Molecular classification based on liquid biopsy showed 87.5% accuracy in correlating with tissue results. Moreover, 65% of cases exhibited ≥1 actionable alteration, including 25% ESCAT I alterations and 13% ESCAT II alterations. Consequently, 16% of patients received a molecularly matched therapy, and presented with a 56% response rate and median progression‐free survival of 7.7 months.

Conclusions

cfDNA sequencing in EC is a feasible approach that produces informative results in 89% of cases and accurately categorizes patients into the main molecular subclasses. It also reveals multiple actionable alterations, which offers the potential for personalized therapeutic strategies.
The association between social vulnerability and geriatric assessment impairments among older adults with gastrointestinal cancers—The CARE Registry
Authors: Fowler Mackenzie E. , Harmon Christian , Tucker Abigail , Sharafeldin Noha , Oates Gabriela , Baker Elizabeth , Nassel Ariann , Giri Smith , Williams Grant R.
Published: June 2024

Background

Older adults comprise the majority of patients with gastrointestinal (GI) cancer. Geriatric assessments (GAs) are recommended for older adults with cancer in part to detect aging‐related impairments (e.g., frailty) associated with early mortality. Social factors like social vulnerability may also influence aging‐related impairments. However, the association between social vulnerability and aging outcomes among older adults with cancer is understudied.

Methods

The authors included 908 older adults aged 60 years and older who were recently diagnosed with GI cancer undergoing GA at their first prechemotherapy visit to the University of Alabama at Birmingham oncology clinic. The primary exposure of interest was the social vulnerability index (SVI). Outcomes were frailty (frail vs. robust/prefrail) and total number of GA impairments (range, 0–13). The authors examined the association between SVI and outcomes using Poisson regression with robust variance estimation and generalized estimating equations.

Results

The median age at GA was 69 years (interquartile range, 64–75 years), 58.2% of patients were male, 22.6% were non‐Hispanic Black, 29.1% had colorectal cancer, 28.2% had pancreatic cancer, and 70.3% had stage III/IV disease. Adjusting for age, sex, cancer type, and disease stage, each decile increase in the SVI was associated with an 8% higher prevalence of frailty (prevalence ratio, 1.08; 95% confidence interval, 1.05–1.11) and a 4% higher average count of total GA impairments (risk ratio, 1.04; 95% confidence interval, 1.02–1.06). The results were attenuated after further adjustment for race and education.

Conclusions

Greater social vulnerability was associated with a higher prevalence of frailty and an increasing average number of GA impairments among older adults with GI cancers before systemic treatment. Intervening on social vulnerability may be a target for improving the risk of frailty and GA impairments, but associations of race and education should be further evaluated.
Alcohol intake and endogenous sex hormones in women: Meta‐analysis of cohort studies and Mendelian randomization
Authors: Tin Tin Sandar , Smith‐Byrne Karl , Ferrari Pietro , Rinaldi Sabina , McCullough Marjorie L. , Teras Lauren R. , Manjer Jonas , Giles Graham , Le Marchand Loïc , Haiman Christopher A. , Wilkens Lynne R. , Chen Yu , Hankinson Sue , Tworoger Shelley , Eliassen A. Heather , Willett Walter C. , Ziegler Regina G. , Fuhrman Barbara J. , Sieri Sabina , Agnoli Claudia , Cauley Jane , Menon Usha , Fourkala Evangelia Ourania , Rohan Thomas E. , Kaaks Rudolf , Reeves Gillian K. , Key Timothy J.
Published: June 2024

Background

The mechanisms underlying alcohol‐induced breast carcinogenesis are not fully understood but may involve hormonal changes.

Methods

Cross‐sectional associations were investigated between self‐reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta‐analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984).

Results

Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two‐sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6–7.6) and free testosterone (7.8%; 4.1–11.5), and an inverse association with SHBG (–8.1%; –11.3% to –4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively).

Conclusions

Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.
Somatostatin receptor 2A expression in von Hippel‐Lindau–related hemangioblastomas
Authors: Ahmad Saya , Muhlebner Angelika , Snijders Tom J. , de Leng Wendy W. , Seute Tatjana , van Leeuwaarde Rachel S.
Published: June 2024

Background

Central nervous system hemangioblastomas are the most prevalent manifestation of von Hippel‐Lindau (VHL) disease and remain the main cause of mortality. Surgical resection is the primary treatment strategy, but is not always possible, and should be used as restrictively as possible. There is an unmet need for less invasive treatment strategies, such as targeted therapy. Expression of somatostatin receptor 2A (SSTR2A) in VHL‐related hemangioblastomas has been described earlier, but the extent of expression in a larger population has yet to be determined. The authors hypothesize that a substantial subset of VHL‐related hemangioblastomas show SSTR2A expression, which may serve as a potential new treatment target.

Methods

Patients who were surgically treated for a VHL‐related hemangioblastoma from 1990 until 2021 at the UMC Utrecht were included. Clinical data was derived from a clinical database. Tissue samples were histopathologically examined with use of hematoxylin and eosin staining, and immunohistochemical analysis of SSTR2A expression was performed.

Results

Forty‐three tissue samples were obtained from 26 patients. Nine showed strong positivity for SSTR2A expression, whereas 13 showed moderate and 15 sparse expression. Three samples showed no expression of SSTR2A. The distribution showed right‐skewedness favoring a strong expression. SSTR2A expression colocalized with endothelial markers and not with stromal cells. Additionally, within‐patient variability for SSTR2A expression was described in 14 patients.

Conclusion

SSTR2A is expressed in varying degrees in the majority of VHL‐related hemangioblastomas. Future treatment with somatostatin analogues or even peptide receptor radionuclide treatment may be considered for SSTR2A‐positive cases.
Use of ultrasensitive RNA in situ hybridization for kappa and lambda light chains assists in the differential diagnosis of B‐cell non‐Hodgkin and Hodgkin lymphomas in cytopathology practice
Authors: Kaseb Hatem , Davey Diane Davis
Published: June 2024

Ultrasensitive RNA in situ hybridization for light chain is a relatively new diagnostic tool that aids in the diagnosis of B‐cell lymphomas. The approach has been shown to be as sensitive as flow cytometry in assessing light chain restriction.
An isolated bidirectional interleaved converter with coupled inductors and active clamp for energy storage systems
Authors: Tseng Kuo‐Ching , Hsiung Hsin‐Yuan , Huang Guan‐Yu
Published: June 2024

A high conversion gain, isolated bidirectional converter for energy storage system is presented. Two coupled inductors stored energy and reduced the current ripple in low‐voltage side. Two coupled inductors are combined with the transformer can increase the voltage conversion ratio and achieve galvanic isolation. Additionally, the energy of the leakage inductance can be recycled into an active clamp capacitor to reduce voltage spikes on the switches. In the high‐voltage side, a voltage‐doubler circuit is used to extend the voltage gain. Finally, the prototype circuit 24 V on the low‐voltage side, 400 V on the high‐voltage side and a rated power of 1 kW is implemented to verify the feasibility of the proposed topology. The experimental results show that the maximum efficiencies in the step‐up and step‐down modes are 97.29% and 96.1% respectively, and the measured full‐load efficiencies are, respectively, 96.62% and 95.68%.
Time In Tight Range in children and adolescents with type 1 diabetes: A cross‐sectional observational single centre study evaluating efficacy of new advanced technologies
Authors: Schiaffini Riccardo , Lumaca Alessandra , Martino Mariangela , Rapini Novella , Deodati Annalisa , Amodeo Maria Elisa , Ciampalini Paolo , Matteoli Maria Cristina , Pampanini Valentina , Cianfarani Stefano
Published: June 2024

Introduction

Early and tight glycaemic control is crucial to prevent long‐term complications of Type 1 Diabetes (T1D). The aim of our study was to compare glucose metrics, including Time In Tight Range (TITR), in a real‐world setting.

Methods

We performed a single‐centre cross‐sectional study in 534 children and adolescents with T1D. Participants were divided into four groups (multiple daily injections + real‐time Continuous glucose monitoring (CGM), multiple daily injections + intermittently scanned CGM, sensor augmented pump (SAP), and Advanced Hybrid Closed‐Loop (AHCL). Demographical and clinical data were collected and analysed.

Results

The group with AHCL showed significantly higher Time In Range (TIR) (71.31% ± 10.88) than SAP (57.82% ± 14.98; p < 0.001), MDI + rtCGM (54.56% ± 17.04; p < 0.001) and MDI + isCGM (52.17% ± 19.36; p < 0.001) groups with a lower Time Above Range (p < 0.001). The group with AHCL also showed lower Time Below Range than MDI + isCGM and SAP groups (p < 0.01). The overall TITR was 37% ± 14 with 19% of participants who reached a TITR ≥50% with a mean TIR of 81%. AHCL had significantly higher TITR (45.46% ± 11.77) than SAP (36.25% ± 13.53; p < 0.001), MDI + rtCGM (34.03% ± 13.89; p < 0.001) and MDI + isCGM (33.37% ± 15.84; p < 0.001) groups with a lower Coefficient of Variation (p < 0.001).

Conclusions

Our study indicates that AHCL ensures a better glycaemic control with an improvement in both TIR and TITR, along with a reduction in CV. Implementation of automated insulin delivery systems should be considered in the treatment of children and adolescents with T1D.
Epigenetic regulation of innate lymphoid cells
Authors: Sun Hanxiao , Qiu Jinxin , Qiu Ju
Published: June 2024

Innate lymphoid cells (ILCs) lack antigen‐specific receptors and are considered the innate arm of the immune system, phenotypically and functionally mirroring CD4+ helper T cells. ILCs are categorized into groups 1, 2, and 3 based on transcription factors and cytokine expression. ILCs predominantly reside in mucosal tissues and play important roles in regional immune responses. The development and function of ILC subsets are controlled by both transcriptional and epigenetic mechanisms, which have been extensively studied in recent years. Epigenetic regulation refers to inheritable changes in gene expression that occur without affecting DNA sequences. This mainly includes chromatin status, histone modifications, and DNA methylation. In this review, we summarize recent discoveries on epigenetic mechanisms regulating ILC development and function, and how these regulations affect disease progression under pathological conditions. Although the ablation of specific epigenetic regulators can cause global changes in corresponding epigenetic modifications to the chromatin, only partial genes with altered epigenetic modifications change their mRNA expression, resulting in specific outcomes in cell differentiation and function. Therefore, elucidating epigenetic mechanisms underlying the regulation of ILCs will provide potential targets for the diagnosis and treatment of inflammatory diseases.
A real‐life study of daratumumab combinations in newly diagnosed patients with light chain (AL) amyloidosis
Authors: Bellofiore Claudia , Benvenuti Pietro , Mina Roberto , Basset Marco , Foli Andrea , Nanci Martina , Nuvolone Mario , Guida Gianluigi , Attanasio Andrea , Mussinelli Roberta , Mangiacavalli Silvia , Cartia Claudio Salvatore , Masoni Valeria , Palumbo Michele , Cani Lorenzo , Oliva Stefania , Consoli Ugo , Conticello Concetta , Di Raimondo Francesco , Arcaini Luca , Bringhen Sara , Merlini Giampaolo , Palladini Giovanni , Milani Paolo
Published: June 2024

Daratumumab‐based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real‐world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6 months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, p 0.955) likewise the rate of cardiac (33% vs. 30%, p 0.340) and renal (40% vs. 16%, p 0.908) responses. Daratumumab‐based regimens demonstrated to be safe and effective in treatment‐naïve AL amyloidosis even in advanced stage disease.
Systemic mechanism of Panax noteginseng saponins in antiaging based on network pharmacology combined with experimental validation
Authors: Zhao Yang‐Yang , Yang Li‐Xia , Que Shuang‐Yu , An Lei‐Xing , Teeti Abeer A. , Xiao Shun‐Wu
Published: June 2024

This study aims to investigate the systemic mechanism of Panax notoginseng saponins (PNS) in antiaging using network pharmacology combined with experimental validation. String database and Cytoscape3.7.2 were used to perform the protein–protein interaction (PPI) and construct genes network. The key target genes were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, the aging‐related genes were verified by reverse‐transcription polymerase chain reaction in SAM‐P/8 mice, and performed molecular docking with the main components of PNS. Moreover, it produced cluster between Hub genes and differential genes. A total of 169 crossover genes were obtained, and the results of GO and KEGG indicated that the antiaging effect of PNS was mediated by apoptosis, cancer, and neurodegeneration and that five of the eight Hub genes had good binding activity with the main components of PNS. In addition, animal experiments reported that MAP2, MAPKK4, RAB6A, and Sortilin‐1 have different levels of expression in the brain tissues of aging mice, and bind well docking with the main active components of PNS. However, there was no crossover between the 169 PNS intersecting genes and the four differential genes, while they yielded a link from PPI in which MAP2K4 was only linked to AKT1 and CASP3; MAP2 was only linked to AKT1 and CASP3; RAB6A was only linked to AKT1; but Sortlin‐1 did not link to the Hub genes. In summary, the antiaging effect of PNS is associated with the eight Hub genes and four differential genes. All of them consist of a cluster or group that is possibly related to the antiaging effect of PNS.
The transition from physical sibling abuse to bullying perpetration through trait anger: A longitudinal study
Authors: I. Lawrence Timothy , Wojciechowski Thomas , Fitzgerald Michael , T. Watson Stephen
Published: June 2024

Objectives

Experiencing physical sibling abuse is a form of family violence that is common but understudied. While it is often perceived as a normative aspect of sibling relationships, there are apparent behavioral consequences. The current study aims to advance the literature by utilizing the displaced aggression model and I3 theory to longitudinally examine trait anger as a pathway linking physical sibling abuse to bullying perpetration.

Methods

Using data from the Bullying, Sexual, and Dating Violence Trajectories from Early to Late Adolescence in the Midwestern United States, 2008–2013, adolescents (n = 851, M = 14.8 years) completed questionnaires at baseline and were reassessed 6 months later.

Results

Results suggested that when adolescents experience physical sibling abuse, they are more likely to engage in bullying perpetration. Mediation analyses indicated that as adolescents were physically abused by a sibling at home, they were more likely to report higher levels of trait anger, which subsequently increased their risk of engaging in bullying perpetration.

Conclusion

These results suggest that experiencing physical sibling abuse has long‐term detrimental consequences, including elicitation of trait anger, subsequently predicting bullying perpetration.
From pill to pain: Alendronate‐induced esophageal injury—A case report and review
Authors: Fan Zhen , Khizar Hayat , Lu Jinjiao , Wang Anhua , Xun Tong , Zhang Xiao , Zhao Hongfeng
Published: June 2024

Background

Alendronate is used to treat Paget's bone disease, glucocorticoid‐induced osteoporosis, and postmenopausal osteoporosis because it suppresses osteoclast activity to stop bone resorption.

Case report

We present an exceptional case of esophagitis caused by alendronate. Blood tests and other data were normal when the patient was taken to the hospital, but an endoscopic examination revealed significant esophageal redness, erosion, and ulceration, along with pseudomembrane. The patient was given medicine after receiving a diagnosis of alendronate pill‐induced esophagitis based on the pathological findings.

Conclusion

This case report is a timely reminder of the importance of thorough pharmacovigilance, patient education, and smart therapeutic decision‐making in the context of alendronate use. To properly treat and prevent problems with the esophagus caused by alendronate, additional research is required.
MELD3.0 is superior to MELDNa and MELD for prediction of mortality in patients with cirrhosis: An external validation in a multi‐ethnic population
Authors: Lin Hong‐Yi , Loi Pooi Ling , Ng Jeanette , Shen Liang , Teo Wei‐Quan , Chung Amber , Raj Prema , Chang Jason Pik‐Eu
Published: June 2024

Background and Aim

The model for end‐stage liver disease (MELD) was updated to MELDNa and recently to MELD3.0 to predict survival of cirrhotic patients. We validated the prognostic performance of MELD3.0 and compared with MELDNa and MELD amongst cirrhotic inpatients.

Methods

Demographical, clinical, biochemical, and survival data of cirrhotic inpatients in Singapore General Hospital (SGH) from 01 January 2018 to 31 December 2018, were studied retrospectively. Patients were followed up from first admission in 2018 until death or until 01 April 2023. Area under the receiver operating characteristic curves (AUROC) were computed for the discriminative effects of MELD3.0, MELDNa, and MELD to predict 30‐, 90‐, and 365‐day mortalities. AUROC was compared with DeLong's test. The cutoff MELD3.0 score for patients at high risk of 30‐day mortality was determined using Youden's Index. Survival curves of patients with MELD3.0 score above and below the cutoff were estimated with Kaplan–Meier method and compared with log‐rank analysis.

Results

Totally 862 patients were included (median age 71.0 years [interquartile range, IQR: 64.0–79.0], 65.4% males, 75.8% Chinese). Proportion of patients with Child‐Turcotte‐Pugh classes A/B/C were 55.5%/35.5%/9.0%. Median MELD3.0/MELDNa/MELD scores were 12.2 (IQR: 8.7–18.3)/11.0 (IQR: 8.0–17.5)/10.3 (IQR: 7.8–15.0). Median time of follow‐up was 51.9 months (IQR: 8.5–59.6). The proportion of 30‐/90‐/365‐day mortalities was 5.7%/13.2%/26.9%. AUROC of MELD3.0/MELDNa/MELD in predicting 30‐, 90‐, and 365‐day mortalities, respectively, were 0.823/0.793/0.783, 0.754/0.724/0.707, 0.682/0.654/0.644 (P < 0.05). Optimal cutoff to predict 30‐day mortality was MELD3.0 > 19 (sensitivity = 67.4%, specificity = 82.4%). Patients with MELD3.0 > 19, compared with patients with MELD3.0 ≤ 19, had shorter median time to death (98.0 days [IQR: 28.8–398.0] vs 390.0 days [IQR: 134.3–927.5]), and higher proportion of 30‐day mortality (68.8% vs 43.0%) (P < 0.001).

Conclusion

MELD3.0 performs better than MELDNa and MELD in predicting mortality in cirrhotic inpatients. MELD3.0 > 19 predicts higher 30‐day mortality.
Impact of tumor proximity to vessel on conversion in laparoscopic liver resection: A retrospective cohort study
Authors: Sakamoto Akimasa , Ogawa Kohei , Shine Mikiya , Nishi Yusuke , Nagaoka Tomoyuki , Honjo Masahiko , Tamura Kei , Sakamoto Katsunori , Funamizu Naotake , Takada Yasutsugu
Published: June 2024

Background

Although various difficulty scoring systems have been proposed for laparoscopic liver resection (LLR), details remain uncertain regarding distance between the tumor and vessels as a factor of difficulty. We aimed to examine the risk factors for conversion to open hepatectomy in LLR, including distance between tumor and vessels.

Methods

Between January 2012 and December 2022, 118 patients who underwent LLR were retrospectively enrolled and their perioperative characteristics were evaluated.

Results

A total of 10 cases (8.5%) were converted to open hepatectomy during LLR. The conversion group had lower platelet count, shorter distance between the tumor and a medium vessel (defined as diameter of 5–10 mm), and greater tumor depth compared with the pure LLR group. Receiver‐operating characteristic curve analysis identified 10 mm as the optimal cutoff value of tumor proximity to a medium vessel (sensitivity, 80.0%, specificity, 78.7%, AUC 0.817) for predicting conversion. In multivariate analysis, lower platelet count (p = .028) and tumor proximity within 10 mm to a medium vessel (p = .001) were independent risk factors for conversion in LLR.

Conclusions

Our study suggests tumor proximity within 10 mm to a medium vessel and lower platelet count as predictors of unfavorable intraoperative conversion in LLR.
Visibility of the biliary orifice after precut papillotomy: Comparison between white light imaging and texture and color enhancement imaging
Authors: Toyonaga Haruka , Kin Toshifumi , Yamazaki Hajime , Ando Ryo , Iwano Kosuke , Nakamura Risa , Ishii Tatsuya , Hayashi Tsuyoshi , Takahashi Kuniyuki , Katanuma Akio
Published: June 2024

Background

Precut papillotomy is performed in cases of difficult biliary cannulation, but identification of the biliary orifice is difficult. Texture and color enhancement imaging (TXI) can enhance the structure, color, and brightness. This study compared TXI and white light imaging (WLI) in visibility of biliary orifices.

Methods

We retrospectively examined 20 patients who underwent bile duct cannulation using both WLI and TXI after precut papillotomy at our center between 2021 and 2022. On WLI and TXI images displayed in random order, bile duct orifice on precut‐incision surface of each image was independently evaluated by eight evaluators. Single‐indication accuracy rate of biliary orifices, visibility score rated on a 4‐grade scale, and color difference between the biliary orifice and the surrounding tissue were examined.

Results

The single‐indication accuracy rate was higher in TXI compared to WLI (50.6% vs. 35.6%, odds ratio 2.26 [95% CI: 1.32–3.89], p = .003). The time to indicate the biliary orifice was comparable between TXI and WLI (median, 9.7 s [range, 2.6–43] vs. 10.9 s [1.5–64], p = .086). Furthermore, the visibility score was higher in TXI than in WLI (median, 3 [interquartile range, 2–3] vs. 2 [2, 3], p < .001), and the color difference between the biliary orifice and surrounding tissue in TXI was more pronounced than in WLI (median, 22.9 [range, 9.39–55.2] vs. 18.0 [6.48–43.0]; p < .001).

Conclusions

TXI enhanced the color difference and visibility of the biliary orifice after precut and improved single‐indication accuracy rate, suggesting that it could be useful for biliary cannulation after precut papillotomy.
Recent advances in TBHP‐promoted heterocyclic ring construction via annulation/cyclization
Authors: Varala Ravi , Seema Vittal , Amanullah Mohammed , Alam Mohammed Mujahid
Published: June 2024

One of the most often utilized hydroperoxides in an array of oxidation strategies is tert‐butyl hydroperoxide (tBuOOH, TBHP). The key reasons for rising utility of TBHP are its low cost, environmental friendliness, high efficiency, and ability to replace hazardous or rare heavy metal oxidants. In this sexennial update, we concisely and critically discussed the applications of TBHP in heterocyclic ring formations starting from 2018 to date. Merits and demerits of its utility, scope of a synthetic organic transformation along with mechanistic logistics are the key features of this review.
Real‐world use of glucocorticoids and clinical outcomes in adults hospitalized with community‐acquired pneumonia on medical wards
Authors: Malecki Sarah , Loffler Anne , Liao Fangming , Hora Tejasvi , Agarwal Arnav , Lail Sharan , Roberts Surain B. , McFadden Derek , Gupta Samir , Razak Fahad , Verma Amol A.
Published: June 2024

Background

Little is known about the real‐world use of systemic glucocorticoids to treat patients hospitalized with community‐acquired pneumonia (CAP) outside of the intensive care unit (ICU).

Methods

This retrospective cohort study included 11,588 hospitalizations for CAP without chronic pulmonary disease at seven hospitals in Ontario, Canada. We report physician‐level variation in the use of glucocorticoids and trends over time. We investigated the association between glucocorticoid prescriptions and clinical outcomes, using propensity score overlap weighting to account for confounding by indication.

Results

Glucocorticoids were prescribed in 1283 (11.1%) patients, increasing over time from 10.0% in 2010 to 11.9% in 2020 (p = .008). Physician glucocorticoid prescribing ranged from 2.9% to 34.6% (median 10.0%, inter quartile range [IQR]: 6.7%–14.6%). Patients receiving glucocorticoids tended to be younger (median age 73 vs. 79), have higher Charlson comorbidity scores (score of 2 or more: 42.4% vs. 31.0%), more cancer (26.6% vs. 13.2%), more renal disease (11.5% vs. 6.6%), and less dementia (7.8% vs. 14.8%). Patients treated with glucocorticoids had higher rates of in‐hospital mortality (weighted Risk Difference = 1.72, 95% confidence interval [95% CI]: 0.16–3.3, p = .033). Glucocorticoid use was not associated with ICU admission, hospital length‐of‐stay, or 30‐day readmission.

Conclusion

Glucocorticoids were prescribed in 11.1% of patients hospitalized with CAP outside of ICU and one in four physicians prescribed glucocorticoids in more than 14% of patients. Glucocorticoid use was associated with greater in‐hospital mortality, although these findings are limited by large selection effects. Clinicians should exercise caution in prescribing glucocorticoids for nonsevere CAP, and definitive trials are needed in this population.
Organized precipitation and associated large‐scale circulation patterns over the Kingdom of Saudi Arabia
Authors: Luong Thang M. , Dasari Hari P. , Doan Quang‐Van , Alduwais Abdulilah K. , Hoteit Ibrahim
Published: June 2024

The Kingdom of Saudi Arabia (KSA) is characterized by a desert climate, with rainfall mainly occurring during the cooler months (November–April) and sometimes in conjunction with intense extratropical systems that can cause serious damage and casualties. Given the vast size of KSA, there are gaps in understanding the association between large‐scale atmospheric circulations and local organized rainfall events, and in characterizing the diversity of this association. To address these gaps, we analyse an in‐house 5‐km horizontal grid spacing regional atmospheric reanalysis that has been specifically generated for the Arabian Peninsula to explore the mechanisms behind the organized rainfall events over KSA. Nine major regions with distinct climate regimes were objectively selected to represent KSA rainfall climatology. The results demonstrate that organized thunderstorms over KSA only occur under sufficient moisture and environmental instabilities. Mesoscale convective systems responsible for organized rainfall generally develop and propagate with low‐level moisture flow from the nearby seas (the Red Sea to the west and Arabian Gulf to the east) toward the desert. In the central part of KSA, the most frequent physical mechanism responsible for rainfall is winter extratropical influence, followed by spring extratropical–tropical interactions, and spring tropical influence. The east coast is characterized by two rainfall modes: a continuous southwest–northeast rain corridor and concentrated southwestern rain. Large‐scale organized convection following three physically distinct mechanisms (extratropical, transition and tropical) is revealed along the west coast.
Beyond weakness: Exploring intramuscular fat and quadriceps atrophy in ACLR recovery
Authors: White McKenzie S. , Ogier Augustin C. , Chenevert Thomas L. , Zucker Elizabeth , Stoneback Luke , Michel Constance P. , Palmieri‐Smith Riann M. , Lepley Lindsey K.
Published: June 2024

Muscle weakness following anterior cruciate ligament reconstruction (ACLR) increases the risk of posttraumatic osteoarthritis (OA). However, focusing solely on muscle weakness overlooks other aspects like muscle composition, which could hinder strength recovery. Intramuscular fat is a non‐contractile element linked to joint degeneration in idiopathic OA, but its role post‐ACLR has not been thoroughly investigated. To bridge this gap, we aimed to characterize quadriceps volume and intramuscular fat in participants with ACLR (male/female = 15/9, age = 22.8 ± 3.6 years, body mass index [BMI] = 23.2 ± 1.9, time since surgery = 3.3 ± 0.9 years) and in controls (male/female = 14/10, age = 22.0 ± 3.1 years, BMI = 23.3 ± 2.6) while also exploring the associations between intramuscular fat and muscle volume with isometric strength. Linear mixed effects models assessed (I) muscle volume, (II) intramuscular fat, and (III) strength between limbs (ACLR vs. contralateral vs. control). Regression analyses were run to determine if intramuscular fat or volume were associated with quadriceps strength. The ACLR limb was 8%−11% smaller than the contralateral limb (p < 0.05). No between‐limb differences in intramuscular fat were observed (p = 0.091−0.997). Muscle volume but not intramuscular fat was associated with strength in the ACLR and control limbs (p < 0.001−0.002). We demonstrate that intramuscular fat does not appear to be an additional source of quadriceps dysfunction following ACLR and that muscle size only explains some of the variance in muscle strength.
Large‐Scale Lensless Microscopy with Fast Acquisition and Region‐Wise Focusing
Authors: Zhou You , Song Weizhi , Wu Linyuan , Fan Lin , Wang Junjia , Jiang Shaowei , Ma Zhan , Xiong Bo , Cao Xun
Published: June 2024

Lensless microscopy provides a wide field of view (FOV) determined by the image sensor size, allowing visualization of large sample areas. Coupled with advanced and even pixel super‐resolution phase retrieval algorithms, it can achieve resolutions up to the sub‐micron level, enabling both large‐FOV and high‐resolution imaging. However, high‐throughput lensless imaging encounters challenges in rapid data acquisition and large‐scale phase retrieval. Furthermore, when examining biological samples over a large FOV, focal plane inconsistencies often emerge among distinct regions. This study introduces a fast acquisition and efficient reconstruction method for coherent lensless imaging. Multiple measurements are manually modulated using an axial translation stage and sequentially captured by an image sensor, requiring no hardware synchronization. Optical parameter calibration, region‐wise auto‐focusing, and region‐wise phase retrieval algorithms are integrated to establish a general parallel computing framework for rapid, efficient, and high‐throughput lensless imaging. Experimental results demonstrate a 7.4 mm × 5.5 mm FOV and 1.38 µm half‐pitch resolution imaging of human skin and lung tumor sections with region‐wise focusing, requiring ≈0.5‐s acquisition time and 17‐s reconstruction time. By incorporating pixel super‐resolution, a 0.98 µm half‐pitch resolution is achieved in full‐FOV peripheral blood smears without additional data required, advantageous for discerning hollow shapes and segmenting blood cells.