bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances on two serological assays for human papillomavirus provide insights on the reactivity of antibodies against a cross-neutralization epitope of the minor capsid protein L2
Authors: Mariz Filipe Colaco , Putzker Kerstin , Sehr Peter , Müller Martin
Published: November 2023

Introduction

A second generation of prophylactic human papillomavirus (HPV) vaccines based on the minor capsid protein L2 has entered clinical trials as promising alternative to meet the gaps left out by the current vaccines concerning type-restricted protection, high costs and low penetrance in immunization programs of lowand middle-income countries. Most of the serological assays available to assess anti-HPV humoral responses are, however, not well suited for measuring vaccine-induced anti-L2 antibody responses.

Methods

In this work, we have advanced our automated, purely add-on High-Throughput Pseudovirion-Based Neutralization Assay (HT-PBNA) in an L2-oriented approach for measuring antibody-mediated neutralization of HPV types 6/16/18/31/33/52/58.

Results and discussion

With the optimized settings, we observed 24- to 120-fold higher sensitivity for detection of neutralizing Ab to the L2 protein of HPV6, HPV16, HPV18, and HPV31, compared to the standard HT-PBNA. Alternatively, we have also developed a highly sensitive, cell-free, colorimetric L2-peptide capture ELISA for which the results were strongly concordant with those of the advanced neutralization assay, named HT-fc-PBNA. These two high-throughput scalable assays represent attractive approaches to determine antibody-based correlates of protection for the HPV L2 vaccines that are to come.
Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse
Authors: Moamin Mohammed Ridha , Allen Richard , Woods Steven Leslie , Brown Janet Elizabeth , Nunns Harry , Juncker-Jensen Anna , Lewis Claire Elizabeth
Published: November 2023

Introduction

Patients with high-risk, triple negative breast cancer (TNBC) often receive neoadjuvant chemotherapy (NAC) alone or with immunotherapy. Various single-cell and spatially resolved techniques have demonstrated heterogeneity in the phenotype and distribution of macrophages and T cells in this form of breast cancer. Furthermore, recent studies in mice have implicated immune cells in perivascular (PV) areas of tumors in the regulation of metastasis and anti-tumor immunity. However, little is known of how the latter change during NAC in human TNBC or their impact on subsequent relapse, or the likely efficacy of immunotherapy given with or after NAC.

Methods

We have used multiplex immunofluorescence and AI-based image analysis to compare the immune landscape in untreated and NAC-treated human TNBCs. We quantified changes in the phenotype, distribution and intercellular contacts of subsets of tumor-associated macrophages (TAMs), CD4+ and CD8+ T cells, and regulatory T cells (Tregs) in PV and non-PV various areas of the stroma and tumor cell islands. These were compared in tumors from patients who had either developed metastases or were disease-free (DF) after a three-year follow up period.

Results

In tumors from patients who remained DF after NAC, there was a marked increase in stromal CD163+ TAMs, especially those expressing the negative checkpoint regulator, T-cell immunoglobulin and mucin domain 3 (TIM-3). Whereas CD4+ T cells preferentially located to PV areas in the stroma of both untreated and NAC-treated tumors, specific subsets of TAMs and Tregs only did so only after NAC. Distinct subsets of CD4+ and CD8+ T cells formed PV clusters with CD163+ TAMs and Tregs. These were retained after NAC.

Discussion

Quantification of stromal TIM-3+CD163+ TAMs in tumor residues after NAC may represent a new way of identifying patients at high risk of relapse. PV clustering of immune cells is highly likely to regulate the activation and function of T cells, and thus the efficacy of T cell-based immunotherapies administered with or after NAC.
Net-phytoplankton communities and influencing factors in the Antarctic Peninsula region in the late austral summer 2019/2020
Authors: Liu Lu , Zhang Jichang , Zhao Yunxia , Luan Qingshan , Zhao Xianyong , Wang Xinliang
Published: November 2023

The waters near the Antarctic Peninsula are characterized with unique oceanographic conditions and rich krill resources. Based on samples collected around the South Shetland Islands (SSI) in austral summer of 2019/2020, the net- phytoplankton community structure and relevant major biotic and abiotic influencing factors were investigated. Eighty-one taxa were identified by light microscope, and diatoms were the most abundant group. The most abundant species were Chaetoceros atlanticus, C. criophilus, C. dichaeta, Fragilariopsis kerguelensis and Pseudo−nitzschia lineola. The abundance and Shannon-Weaver index of net-phytoplankton ranged from 100 to 2.64×107 cells/m3 and 0.0747 to 4.0176 respectively, with significantly low values detected in the Bransfield Strait (BS) and high values in the west of the SSI. The dissimilarity was mainly caused by the differences in abundance of diatoms (including Thalassiothrix antarctica and the species in genus Rhizosolenia, Chaetoceros, Fragilariophsis). These diatoms and Dictyocha speculum were found in higher abundance in the west of the SSI, while Corethron pennatum and cryptophytes were found in higher abundance in the BS. Combined with acoustic density of krill and environmental data (Sea Surface Temperature and Sea Ice Concentration). The multivariate analysis suggested that phytoplankton community was positively affected by the SST, and the acoustic- derived krill density would be associated with the spatial distribution of pennate diatoms. This study enhances the knowledge about the selective feeding for krill and provides ecological implications for the Antarctic marine ecosystem.
Quantifying conditional probabilities of fish-turbine encounters and impacts
Authors: Peraza Jezella I. , Horne John K.
Published: November 2023

Tidal turbines are one source of marine renewable energy but development of tidal power is hampered by uncertainties in fish-turbine interaction impacts. Current knowledge gaps exist in efforts to quantify risks, as empirical data and modeling studies have characterized components of fish approach and interaction with turbines, but a comprehensive model that quantifies conditional occurrence probabilities of fish approaching and then interacting with a turbine in sequential steps is lacking. We combined empirical acoustic density measurements of Pacific herring (Clupea pallasii) and when data limited, published probabilities in an impact probability model that includes approach, entrainment, interactions, and avoidance of fish with axial or cross-flow tidal turbines. Interaction impacts include fish collisions with stationary turbine components, blade strikes by rotating blades, and/or a collision followed by a blade strike. Impact probabilities for collision followed by a blade strike were lowest with estimates ranging from 0.0000242 to 0.0678, and highest for blade strike ranging from 0.000261 to 0.40. Maximum probabilities occurred for a cross-flow turbine at night with no active or passive avoidance. Estimates were lowest when probabilities were conditional on sequential events, and when active and passive avoidance was included for an axial-flow turbine during the day. As expected, conditional probabilities were typically lower than analogous independent events and literature values. Estimating impact probabilities for Pacific herring in Admiralty Inlet, Washington, United States for two device types illustrates utilization of existing data and simultaneously identifies data gaps needed to fully calculate empirical-based probabilities for any site-species combination.
Medical students on the COVID-19 frontline: a qualitative investigation of experiences of relief, stress, and mental health
Authors: Klasen Jennifer M. , Poljo Adisa , Sortino Rosita , Bogie Bryce J. M. , Schoenbaechler Zoe , Meienberg Andrea , Nickel Christian , Bingisser Roland , LaDonna Kori A.
Published: November 2023

Objective

During the early stages of the COVID-19 pandemic, medical students were abruptly removed from clinical rotations and transitioned to virtual learning. This study investigates the impact of this shift on students’ wellbeing and preparedness for advanced training.

Methods

Through qualitative research methods, including semi-structured interviews, the experiences of medical students working on the COVID-19 frontline were explored.

Results

The comprehensive findings of the study shed light on the profound emotional journey that medical students embarked upon during the relentless public health crisis. Within the chaos and overwhelming demands of the pandemic, medical students discovered a profound sense of purpose and fulfillment in their contributions to the welfare of the community. Despite the personal sacrifices they had to make, such as long hours, limited social interactions, and potentially risking their own health, students reported feelings of relief and gratitude.

Conclusion

Tailored support systems for medical students’ wellbeing are crucial for improving healthcare delivery during crises. Medical schools should adopt a holistic curriculum approach, integrating interdisciplinary learning and prioritizing student wellbeing. Recognizing the pandemic’s impact on students and implementing targeted support measures ensures resilience and contributes to an improved healthcare system.
First insights into multidisciplinary and multispecialty long COVID networks—a SWOT analysis from the perspective of ambulatory health care professionals
Authors: Stengel Sandra , Gölz Lea , Kolb Joachim , Tarbet Karin , Völler Stefanie , Koetsenruijter Jan , Szecsenyi Joachim , Merle Uta
Published: November 2023

Introduction

Multidisciplinary and multispecialty approaches with central integration of primary care, individualized long-term rehabilitative care, and multidisciplinary care pathways are recommended by international consortia to face the challenges of care of long COVID. Two regional long COVID networks—Rhein-Neckar (RN) and Ludwigsburg (LU) have emerged as ad hoc examples of best practice in Southern Germany. The aim of the community case study is to provide first insights into the experiences of the networks.

Methods

The exploratory observational study was conducted between April and June 2023, focusing on an observation period of just under 24 months and using a document analysis supported by MAXQDA and SWOT analysis with ambulatory health care professionals in two online group discussions.

Results

The document analysis revealed that both networks have defined network participants who have agreed on common goals and patient pathways and have established ways of communicating, organizing, and collaborating. Both networks agreed on a primary care-based, multidisciplinary and multispecialty approach. The main differences in realization emerged in LU as a focus on the ambulatory setting and very concrete application to individual patients, while RN showed a focus on an intersectoral character with participation of the specialized university hospital sector, knowledge transfer and a supra-regional approach with the involvement of the meso and macro level. The SWOT analysis (n = 14 participants, n = 6 male, 7 physicians (4 disciplines), 7 therapists (5 professions)) showed strengths such as resulting collaboration, contribution to knowledge transfer, and improvement of care for individual patients. As barriers, e.g., lack of reimbursement, high efforts of care, and persistent motivation gaps became apparent. Potentials mentioned were, e.g., transferability to other diseases such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, promotion of addressing a “difficult topic” and promotion of intersectoral care concepts; risks mentioned were, e.g., limited network resources and negative effects on the development of other structures.

Conclusion

Resulting implications for practice and research address a call to policy makers and funders to support further research to find out what generalizable results regarding usefulness, effectiveness, and efficiency including transferability to other post-infectious diseases can be derived.
Association of direct bilirubin to total bilirubin ratio with 90-day mortality in patients with acute-on-chronic liver failure
Authors: Ma Yuanji , Du Lingyao , Zhou Shaoqun , Bai Lang , Tang Hong
Published: November 2023

Background

Hyperbilirubinemia occurs when the liver fails to process bilirubin properly. A disproportionate increase in direct bilirubin indicates a decreased ability of the hepatocytes to uptake and/or convert bilirubin, which may impact the prognosis of patients with acute-on-chronic liver failure (ACLF). However, the association of direct bilirubin to total bilirubin ratio (DB/TB) with outcomes in patients with ACLF remains unclear.

Methods

A retrospective study was conducted in West China Hospital of Sichuan University to assess the association between DB/TB and 90-day mortality in patients with ACLF. The diagnosis of ACLF was based on the Chinese Group on the Study of Severe Hepatitis B (COSSH) ACLF criteria. Ordinal logistic regression models, linear regression models, and Cox proportional hazards models were applied to evaluate the association between DB/TB and hepatic encephalopathy, disease severity, and outcome, respectively.

Results

A total of 258 patients with ACLF were included. The surviving patients were less likely to have liver cirrhosis and comorbidities, and their disease severities were milder than the dead. DB/TB was negatively correlated to cerebral score for hepatic encephalopathy (adjusted odds ratio: 0.01, p = 0.043), and disease severity (adjusted standardized coefficients: −0.42~−0.31, all p < 0.001), respectively. A significant 90-day mortality risk of DB/TB was observed [all adjusted hazard ratio (aHR) < 0.20 and all p ≤ 0.001]. Compared with patients with DB/TB < 0.80, patients with ACLF and DB/TB ≥ 0.80 had much lower 90-day mortality risk (all aHR < 0.75 and all p < 0.01).

Conclusion

DB/TB could be an independent risk factor to predict the short-term prognosis in patients with ACLF. More attention should be paid to patients with lower DB/TB due to their poorer prognosis and more urgent need for liver transplantation.

Clinical trial registration:http://www.chictr.org.cn/showproj.aspx?proj=56960, identifier, ChiCTR2000035013.
Current trends of clinical trials involving CRISPR/Cas systems
Authors: Zhang Songyang , Wang Yidi , Mao Dezhi , Wang Yue , Zhang Hong , Pan Yihan , Wang Yuezeng , Teng Shuzhi , Huang Ping
Published: November 2023

The CRISPR/Cas9 system is a powerful genome editing tool that has made enormous impacts on next-generation molecular diagnostics and therapeutics, especially for genetic disorders that traditional therapies cannot cure. Currently, CRISPR-based gene editing is widely applied in basic, preclinical, and clinical studies. In this review, we attempt to identify trends in clinical studies involving CRISPR techniques to gain insights into the improvement and contribution of CRISPR/Cas technologies compared to traditional modified modalities. The review of clinical trials is focused on the applications of the CRISPR/Cas systems in the treatment of cancer, hematological, endocrine, and immune system diseases, as well as in diagnostics. The scientific basis underlined is analyzed. In addition, the challenges of CRISPR application in disease therapies and recent advances that expand and improve CRISPR applications in precision medicine are discussed.
Dopamine alters phage morphology to exert an anti-infection effect
Authors: Zhang Shengting , Hu Xiuling , Zhang Chunting , Ju Yani , Liu Xin , Wei Yunlin
Published: November 2023

Antiviral drug development is important for human health, and the emergence of novel COVID-19 variants has seriously affected human lives and safety. A bacteriophage—a bacterial virus with a small and simple structure—is an ideal experimental candidate for studying the interactions between viruses and their hosts. In this study, the effects and mechanisms of catecholamines on phages were explored, and dopamine (DA) was found to have general and efficient anti-infection effects. A clear dose-dependent effect was observed when different phages were treated with DA, with higher DA concentrations exhibiting stronger anti-phage activity. The half maximal inhibitory concentration values of DA for vB-EcoS-IME167, T4 Phage, and VMY22 were determined as 0.26, 0.12, and 0.73 mg mL−1, respectively. The anti-phage effect of DA increased with treatment duration. In addition, the anti-infection activities of DA against vB-EcoS-IME167, T4 Phage, and VMY22 were increased by 105, 104, and 104 folds compared to that of the control. This ability of DA was observed only in phages and not in the host bacteria. Morphological changes of phages were observed under transmission electron microscopy following their treatment with DA, and considerable changes in adsorption were confirmed via quantitative reverse transcription polymerase chain reaction. These results suggest that the anti-phage effect of DA is primarily due to the destruction of the external structure of the phage. This study, to the best of our knowledge, is the first to report the universal anti-phage infection effect of dopamine, which provides novel information regarding DA and forms a basis for further research and development of antiviral drugs. Moreover, it provides a new perspective for the research about the defense and counter-defense of bacteria and bacteriophages.
Composition, antibiotic resistance, and virulence analysis of microbiota in dormitory drain pipes
Authors: Hu Yan , Zhang Kunyuan , Li Nan , Wang Shengqin
Published: November 2023

Introduction

Dormitory washbasins can breed microorganisms that produce odorous gases, polluting the indoor environment.

Methods

We utilized metagenome sequencing to analyze the microbiota of 40 samples from the drain pipes of dormitory washbasins. Our study aimed to investigate the microbial community structure, antibiotic resistance genes, and virulence factors, and to identify potential influencing factors such as gender, hometown, frequency of hand sanitizer usage, and number of dormitory residents.

Results

The analysis revealed 12 phyla and 147 genera, with Proteobacteria and Actinobacteria being the dominant phyla, and Mycobacterium and Nakamurella being the dominant genera. We found that the factors influencing the microbial community structure of the dormitory washbasin drain pipe are complex. The investigated factors have a slight influence on the drain pipe microbial community, with gender exerting a discernible influence. The annotation results revealed the presence of various virulence factors, pathogenic toxins and antibiotic resistance genes, including 246 different toxin types and 30 different types of antibiotic resistance genes. In contrast to the observed differences in microbial composition among samples, the distribution of resistance genes shows relatively small changes among samples. Antibiotics should be a contributing factor in the overall increase of antibiotic resistance genes in drain pipes.

Discussion

Overall, our study provides important insights into the community structure and function of microorganisms in dormitory drainage systems, and can guide efforts to prevent and control microbial pollution.
Cytological studies reveal high variation in ascospore number and shape and conidia produced directly from ascospores in Morchella galilaea
Authors: Du Xi-Hui , Wang Si-Yue , Ryberg Martin , Guo Yong-Jie , Wei Jing-Yi , Pfister Donald H. , Johannesson Hanna
Published: November 2023

Spores are important as dispersal and survival propagules in fungi. In this study we investigated the variation in number, shape, size and germination mode of ascospores in Morchella galilaea, the only species of the genus Morchella known to fruit in the autumn. Based on the observation of five samples, we first discovered significant variation in the shape and size of ascospores in Morchella. One to sixteen ascospores were found in the asci. Ascospore size correlated negatively with ascospore number, but positively with ascus size, and ascus size was positively correlated with ascospore number. We noted that ascospores, both from fresh collections and dried specimens, germinated terminally or laterally either by extended germ tubes, or via the production of conidia that were formed directly from ascospores at one, two or multiple sites. The direct formation of conidia from ascospores takes place within asci or after ascospores are discharged. Using laser confocal microscopy, we recorded the number of nuclei in ascospores and in conidia produced from ascospores. In most ascospores of M. galilaea, several nuclei were observed, as is typical of species of Morchella. However, nuclear number varied from zero to around 20 in this species, and larger ascospores harbored more nuclei. One to six nuclei were present in the conidia. Nuclear migration from ascospores to conidia was observed. Conidia forming directly from ascospores has been observed in few species of Pezizomycetes; this is the first report of the phenomenon in Morchella species. Morphological and molecular data show that conidial formation from ascospores is not found in all the specimens of this species and, hence, is not an informative taxonomic character in M. galilaea. Our data suggest that conidia produced from ascospores and successive mitosis within the ascus may contribute to asci with more than eight spores. The absence of mitosis and/or nuclear degeneration, as well as cytokinesis defect, likely results in asci with fewer than eight ascospores. This study provides new insights into the poorly understood life cycle of Morchella species and more broadly improves knowledge of conidia formation and reproductive strategies in Pezizomycetes.
Populational genomic insights of Paraclostridium bifermentans as an emerging human pathogen
Authors: Cai Xunchao , Peng Yao , Yang Gongli , Feng Lijuan , Tian Xiaojuan , Huang Ping , Mao Yanping , Xu Long
Published: November 2023

Paraclostridium bifermentans (P.b) is an emerging human pathogen that is phylogenomically close to Paeniclostridium sordellii (P.s), while their populational genomic features and virulence capacity remain understudied. Here, we performed comparative genomic analyses of P.b and compared their pan-genomic features and virulence coding profiles to those of P.s. Our results revealed that P.b has a more plastic pangenome, a larger genome size, and a higher GC content than P.s. Interestingly, the P.b and P.s share similar core-genomic functions, but P.b encodes more functions in nutrient metabolism and energy conversion and fewer functions in host defense in their accessory-genomes. The P.b may initiate extracellular infection processes similar to those of P.s and Clostridium perfringens by encoding three toxin homologs (i.e., microbial collagenase, thiol-activated cytolysin, phospholipase C, which are involved in extracellular matrices degradation and membrane damaging) in their core-genomes. However, P.b is less toxic than the P.s by encoding fewer secretion toxins in the core-genome and fewer lethal toxins in the accessory-genome. Notably, P.b carries more toxins genes in their accessory-genomes, particularly those of plasmid origin. Moreover, three within-species and highly conserved plasmid groups, encoding virulence, gene acquisition, and adaptation, were carried by 25–33% of P.b strains and clustered by isolation source rather than geography. This study characterized the pan-genomic virulence features of P.b for the first time, and revealed that P. bifermentans is an emerging pathogen that can threaten human health in many aspects, emphasizing the importance of phenotypic and genomic characterizations of in situ clinical isolates.
Eukaryotic translation initiation factor 4A1 in the pathogenesis and treatment of cancers
Authors: Huang Jinghong , Zhang Lei , Yang Rui , Yao Lixia , Gou Jinming , Cao Dongdong , Pan Zeming , Li Dongmei , Pan Yuanming , Zhang Wei
Published: November 2023

Abnormal translate regulation is an important phenomenon in cancer initiation and progression. Eukaryotic translation initiation factor 4A1 (eIF4A1) protein is an ATP-dependent Ribonucleic Acid (RNA) helicase, which is essential for translation and has bidirectional RNA unwinders function. In this review, we discuss the levels of expression, regulatory mechanisms and protein functions of eIF4A1 in different human tumors. eIF4A1 is often involved as a target of microRNAs or long non-coding RNAs during the epithelial-mesenchymal transition, associating with the proliferation and metastasis of tumor cells. eIF4A1 protein exhibits the promising biomarker for rapid diagnosis of pre-cancer lesions, histological phenotypes, clinical staging diagnosis and outcome prediction, which provides a novel strategy for precise medical care and target therapy for patients with tumors at the same time, relevant small molecule inhibitors have also been applied in clinical practice, providing reliable theoretical support and clinical basis for the development of this gene target.
DNA methylation of the oxytocin receptor interacts with age to impact neural response to social stimuli
Authors: Puglia Meghan H. , Lynch Morgan E. , Nance Madelyn G. , Connelly Jessica J. , Morris James P.
Published: November 2023

Introduction

Social isolation is one of the strongest predictors of increased risk of mortality in older adulthood. The ability to form and maintain the social relationships that mitigate this risk is partially regulated by the oxytocinergic system and one’s ability to attend to and process social information. We have previously shown that an epigenetic change to the DNA of the oxytocin receptor gene (OXTR methylation) affects the salience of social information in young adults. Little is known about how the oxytocinergic system ages and what effect this aging system has on social cognitive abilities throughout the lifespan.

Methods

Here we explored age-related differences in the association between neural response during selective social attention and OXTR DNA methylation in young (age 18–31) and older (age 58-81) adults. Participants underwent fMRI during a selective social attention task and provided a DNA sample for the assessment of OXTR methylation.

Results and Discussion

We found that older adults activated diffuse areas of visual cortex and dorsolateral prefrontal cortex during selective social attention, consistent with the dedifferentiation and compensatory neural activation commonly reported in aging. We found a significant age-by-OXTR methylation interaction on neural response when attending to social stimuli in a complex display; young adults displayed a positive association between OXTR methylation and neural activation, replicating our prior finding that young adults with presumed diminished endogenous access to oxytocin recruit regions of the attentional cortex to a greater extent. This association did not hold for older adults. Instead, perceived social support interacted with OXTR methylation to influence neural response during selective social attention. These data suggest that environmental factors like social support moderate biological processes in aging and highlight the importance of a lifespan perspective for understanding associations between individual differences in the oxytocinergic system, neural function, and social behavior.
Active contact proximity to the cerebellothalamic tract predicts initial therapeutic current requirement with DBS for ET: an application of 7T MRI
Authors: Ikramuddin Salman S. , Brinda Annemarie K. , Butler Rebecca D. , Hill Meghan E. , Dharnipragada Rajiv , Aman Joshua E. , Schrock Lauren E. , Cooper Scott E. , Palnitkar Tara , Patriat Rémi , Harel Noam , Vitek Jerrold L. , Johnson Matthew D.
Published: November 2023

Objective

To characterize how the proximity of deep brain stimulation (DBS) active contact locations relative to the cerebellothalamic tract (CTT) affect clinical outcomes in patients with essential tremor (ET).

Background

DBS is an effective treatment for refractory ET. However, the role of the CTT in mediating the effect of DBS for ET is not well characterized. 7-Tesla (T) MRI-derived tractography provides a means to measure the distance between the active contact and the CTT more precisely.

Methods

A retrospective review was conducted of 12 brain hemispheres in 7 patients at a single center who underwent 7T MRI prior to ventral intermediate nucleus (VIM) DBS lead placement for ET following failed medical management. 7T-derived diffusion tractography imaging was used to identify the CTT and was merged with the post-operative CT to calculate the Euclidean distance from the active contact to the CTT. We collected optimized stimulation parameters at initial programing, 1- and 2-year follow up, as well as a baseline and postoperative Fahn-Tolosa-Marin (FTM) scores.

Results

The therapeutic DBS current mean (SD) across implants was 1.8 mA (1.8) at initial programming, 2.5 mA (0.6) at 1 year, and 2.9 mA (1.1) at 2-year follow up. Proximity of the clinically-optimized active contact to the CTT was 3.1 mm (1.2), which correlated with lower current requirements at the time of initial programming (R2 = 0.458, p = 0.009), but not at the 1- and 2-year follow up visits. Subjects achieved mean (SD) improvement in tremor control of 77.9% (14.5) at mean follow-up time of 22.2 (18.9) months. Active contact distance to the CTT did not predict post-operative tremor control at the time of the longer term clinical follow up (R2 = -0.073, p = 0.58).

Conclusion

Active DBS contact proximity to the CTT was associated with lower therapeutic current requirement following DBS surgery for ET, but therapeutic current was increased over time. Distance to CTT did not predict the need for increased current over time, or longer term post-operative tremor control in this cohort. Further study is needed to characterize the role of the CTT in long-term DBS outcomes.
Consumer acceptance of upcycled craft beer: a New Zealand case study
Authors: Goodman-Smith Francesca , Bhatt Siddharth , Grasso Simona , Deutsch Jonathan , Mirosa Miranda
Published: November 2023

Upcycled foods are created from surplus food, edible food waste and by-products. Food and beverage brands are launching upcycled foods and promoting their product to consumers. Little is known about how consumers respond to upcycled foods, nor how these products can be most effectively promoted. To better understand marketing strategies for upcycled foods, two studies were conducted, one online (n = 300) and one in retail stores (n = 65), in New Zealand to examine differences in consumer sentiment toward upcycled beer. In both studies, environmental benefits were identified as the most important benefits of upcycled foods and information provision on pack and online were important promotional strategies. Consumers reported greater awareness and acceptance of upcycled food in-store, yet raised concerns relating to taste and price. Only 31% of participants surveyed in-store associated ‘no negatives’ with upcycled foods compared with 47% of consumers surveyed online. These findings help differentiate a potential promotion strategy for upcycled foods.
Triple-negative breast cancer: from none to multiple therapeutic targets in two decades
Authors: Carvalho Filomena Marino
Published: November 2023

Triple-negative breast cancers (TNBCs) are more likely to occur in younger patients and have a poor prognosis. They are highly heterogeneous tumors consisting of different molecular subtypes. The only common characteristic among them is the absence of targets for endocrine therapy and human epidermal growth factor receptor 2 (HER2) blockade. In the past two decades, there has been an increased understanding of these tumors from a molecular perspective, leading to their stratification according to new therapeutic strategies. TNBC has ushered breast carcinomas into the era of immunotherapy. The higher frequency of germline BRCA mutations in these tumors enables targeting this repair defect by drugs like PARP inhibitors, resulting in synthetic lethality in neoplastic cells. Additionally, we have the identification of new molecules to which this generation of smart drugs, such as antibody-drug conjugates (ADCs), are directed. In this review, we will discuss the trajectory of this knowledge in a systematic manner, presenting the molecular bases, therapeutic possibilities, and biomarkers.
Metastatic bladder cancer forming a sigmoidorectal fistula after enfortumab vedotin therapy: a case report
Authors: Tamada Shinji , Ikarashi Daiki , Yanagawa Naoki , Toyoshima Moe , Takahashi Kenta , Matsuura Tomohiko , Maekawa Shigekatsu , Kato Renpei , Kanehira Mitsugu , Takata Ryo , Obara Wataru
Published: November 2023

We report the case of a 68-year-old man who developed a sigmoidorectal fistula after marked response to enfortumab vedotin for advanced bladder cancer. The patient had undergone radical cystectomy with ileal conduit after neoadjuvant chemotherapy. Six months after surgery, local recurrence in the pelvic cavity and multiple lung metastases were found, and the patient was administered pembrolizumab as second-line therapy. Due to worsening local recurrence and suspected invasion of the sigmoid colon and rectum, enfortumab vedotin was initiated as third-line therapy and comprehensive genomic profiling was simultaneously performed. Enfortumab vedotin was remarkably effective, the lung metastases disappeared, and the local recurrent lesion shrank in volume although a sigmoidorectal fistula was found to form through the tumor cavity. Immunohistochemical analysis of the tumor specimens exhibited increased nectin-4 expression. This rare case of metastatic bladder cancer with sigmoidorectal fistula associated with effective enfortumab vedotin therapy suggests that nectin-4 expression and comprehensive genomic profiling might be useful in predicting treatment response to enfortumab vedotin.
Tertiary lymphoid structures in gynecological cancers: prognostic role, methods for evaluating, antitumor immunity, and induction for therapy
Authors: Zhang Ke , Xie Xiao , Zheng Shuang-Lin , Deng Yuan-Run , Liao Dan , Yan Hai-Chen , Kang Xi , Jiang Hui-Ping , Guo Sui-Qun
Published: November 2023

Tertiary lymphoid structures (TLSs), referred to as tertiary lymphoid organs and lymphoid tissue neogenesis, are aggregates of immune cells that occur in nonlymphoid tissues. In recent years, it has been found that TLSs within the tumor microenvironment have been associated with local adaptive immune immunity against cancer and favorable prognosis in several human solid tumors, including gynecological cancers. The issue of the prognosis of gynecological cancers, including endometrial, cervical, and ovarian cancer, is an enormous challenge that many clinical doctors and researchers are now facing. Concerning the predictive prognostic role of TLSs, effective evaluation, and quantification of TLSs in human tissues may be used to assist gynecologists in assessing the clinical outcome of gynecological cancer patients. This review summarizes the current knowledge of TLSs in gynecological cancers, mainly focusing on the potential mechanism of TLS neogenesis, methods for evaluating TLSs, their prognostic value, and their role in antitumor immune immunity. This review also discusses the new therapeutic methods currently being explored in gynecological cancers to induce the formation of TLSs.
Outcomes of fertility preservation treatments in patients with endometrial cancer with different molecular classifications based on an NGS panel
Authors: Xu Yan , Zhao Mingming , Zhang Li , Wang Tianyou , Wang Bo , Xue Yu , Xu Zhiying , Shao Wenyu , Chen Xiaojun , Wang Chao
Published: November 2023

Background

The molecular classification of endometrial cancer has previously been shown to be associated with clinical outcomes. However, there are insufficient data to support the routine use of molecular classification for the treatment of patients seeking fertility preservation.

Methods

Here, we retrospectively investigated 90 patients received fertility-sparing treatment. We used a next generation sequencing (NGS) panel to classify these patients into four subtypes. All patients received hormonal therapy combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every three months during the treatment.

Results

Patients with POLE mutations had the highest disease progression rate (50.0%, P=0.013), while the microsatellite instability-high (MSI-H) group had the highest recurrence rate (50.0%, P=0.042). PIK3CA mutation (hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.37–0.99; P=0.046), overweight (HR: 0.56; 95% CI: 0.32–0.96; P=0.033) and obesity (HR: 0.44; 95% CI: 0.20–0.95; P=0.036) were associated with a significantly lower cumulative complete response (CR) rate. The combination of gonadotropin-releasing hormone analogues (GnRH-a) and letrozole (HR: 3.43; 95% CI: 1.81–6.52; P< 0.001) was associated with a significantly higher cumulative CR rate. KRAS mutation was significantly associated with disease progression (P=0.002). In wild-type TP53 patients, PTEN and PIK3CA mutations significantly prolonged the duration of treatment to achieve CR (log rank P=0.034; P=0.018).

Conclusion

The implementation of molecular classification for EC patients undergoing fertility-sparing treatment is promising and can facilitate the selection of appropriate medical regimes to achieve better outcomes in patients with EC who require fertility preservation treatment.
Natural killer cell-related prognosis signature predicts immune response in colon cancer patients
Authors: Li Meiqin , Song Jingqing , Wang Lin , Wang Qi , Huang Qinghua , Mo Dan
Published: November 2023

Background: Natural killer (NK) cells are crucial components of the innate immune system that fight tumors and viral infections. Patients with colorectal cancer (CRC) have a poor prognosis, and immunotherapeutic tools play a key role in the treatment of CRC.

Methods: Public data on CRC patients was collected from the TCGA and the GEO databases. Tissue data of CRC patients were collected from Guangxi Medical University Affiliated Cancer Hospital. An NK-related prognostic model was developed by the least absolute shrinkage and selection operator (LASSO) and Cox regression method. Validation data were collected from different clinical subgroups and an external independent validation cohort to verify the model’s accuracy. In addition, multiple external independent immunotherapy datasets were collected to further examine the value of NK-related risk scores (NKRS) in the prediction of immunotherapy response. Potential biological functions of key genes were examined by methods of cell proliferation, apoptosis and Western blotting.

Results: A novel prognostic model for CRC patients based on NK-related genes was developed and NKRS was generated. There was a significantly poorer prognosis among the high-NKRS group. Based on immune response prediction, patients with low NKRS may be more suitable for immunotherapy and they are more sensitive to immunotherapy. The proliferation rate of CRC cells was significantly reduced and apoptosis of CRC cells was increased after SLC2A3 was knocked down. SLC2A3 was also found to be associated with the TGF-β signaling pathway.

Conclusion: NKRS has potential applications for predicting prognostic status and response to immunotherapy in CRC patients. SLC2A3 has potential as a therapeutic target for CRC.
Bibliometric insights into the most influential papers on antibiotic adjuvants: a comprehensive analysis
Authors: Sun Ke , Xu Ping , Zhang Yu , Yu Pingjing , Ju Yuan
Published: November 2023

Background: The utilization of antibiotic adjuvants presents a promising strategy for addressing bacterial resistance. Recently, the development of antibiotic adjuvants has attracted considerable attention from researchers in academia and industry. This study aimed to identify the most influential publications on antibiotic adjuvants and elucidate the hotspots and research trends in this field.

Method: Original articles and reviews related to antibiotic adjuvants were retrieved from the Web of Science Core Collection database. The top 100 highly cited publications were selected and the visual analyses of publication outputs, countries, institutions, authors, journals, and keywords were conducted using Excel, VOSviewer, or CtieSpace software tools.

Results: The top 100 cited publications concerning antibiotic adjuvants spanned the years 1977–2020, with citation counts ranging from 174 to 2,735. These publications encompassed 49 original articles and 51 reviews. The journal “Antimicrobial Agents and Chemotherapy” accounted for the highest number of publications (12%). The top 100 cited publications emanated from 39 countries, with the United States leading in production. Institutions in Canada and the United States exhibited the most substantial contributions to these highly cited publications. A total of 526 authors participated in these studies, with Robert E.W. Hancock, Laura J. V. Piddock, Xian-Zhi Li, Hiroshi Nikaido, and Olga Lomovskaya emerging as the most frequently nominated authors. The most common keywords included “E. coli”, “P. aeruginosa”, “S. aureus”, “in-vitro activity”, “antimicrobial peptide”, “efflux pump inhibitor” “efflux pump”, “MexAB-OprM” and “mechanism”. These keywords underscored the hotspots of bacterial resistance mechanisms and the development of novel antibiotic adjuvants.

Conclusion: Through the bibliometric analysis, this study identified the top 100 highly cited publications on antibiotic adjuvants. Moreover, the findings offered a comprehensive understanding of the characteristics and frontiers in this field.
Corpus of Mandarin Child Language: a preliminary study on the acquisition of semantic content categories in Mandarin-speaking preschoolers
Authors: Tang Tempo Po-Yi , Lau Dustin Kai-Yan , Leung Man-Tak
Published: November 2023

In studying language acquisition in children, sizable research studies have been focusing on the investigation of form and lexical semantics. This study aims to establish a child language database annotated both syntactically with part of speech and semantically with semantic content category to supplement the study of child language acquisition in the semantic domain beyond lexical level. The Corpus of Mandarin Child Language (CMCL) that documented the production of different semantic content categories by Mandarin-speaking children was established. Naturalistic language samples of 82 native Mandarin-speaking children aged 25–60 months, divided into three age groups, were obtained. The corresponding semantic content categories coded in each utterance were tagged according to previous studies, in addition to the annotations of part of speech. MLU and lexical diversity were examined and the usage and acquisition of different semantic content categories were also analyzed. The results regarding syntactic complexity and lexical diversity replicated the typical language acquisition pattern from previous studies, which supported the validity of the data obtained in the CMCL. To investigate the trajectory of acquisition of various semantic content categories by age, a 90% acquisition criterion was used. Our findings regarding the acquisition order of semantic content category were basically in line with previous studies in general, with some minor differences. This acquisition order observed is largely explained by the cognitive and syntactic complexity associated with the semantic content category, with additional influence from language specific properties and cultural specific factors of Mandarin. In addition, with the tags in both part-of-speech and semantic content category, the CMCL potentially provides a platform for examining the form-content interface in early child language acquisition, which also implies significantly on the theoretical and clinical ground.
Open Dialogue services around the world: a scoping survey exploring organizational characteristics in the implementation of the Open Dialogue approach in mental health services
Authors: Pocobello Raffaella , Camilli Francesca , Alvarez-Monjaras Mauricio , Bergström Tomi , von Peter Sebastian , Hopfenbeck Mark , Aderhold Volkmar , Pilling Stephen , Seikkula Jaakko , el Sehity Tarek Josef
Published: November 2023

Objective

This cross-sectional study investigates the characteristics and practices of mental health care services implementing Open Dialogue (OD) globally.

Methods

A structured questionnaire including a self-assessment scale to measure teams’ adherence to Open Dialogue principles was developed. Data were collected from OD teams in various countries. Confirmatory Composite Analysis was employed to assess the validity and reliability of the OD self-assessment measurement. Partial Least Square multiple regression analysis was used to explore characteristics and practices which represent facilitating and hindering factors in OD implementation.

Results

The survey revealed steady growth in the number of OD services worldwide, with 142 teams across 24 countries by 2022, primarily located in Europe. Referrals predominantly came from general practitioners, hospitals, and self-referrals. A wide range of diagnostic profiles was treated with OD, with psychotic disorders being the most common. OD teams comprised professionals from diverse backgrounds with varying levels of OD training. Factors positively associated with OD self-assessment included a high percentage of staff with OD training, periodic supervisions, research capacity, multi-professional teams, self-referrals, outpatient services, younger client groups, and the involvement of experts by experience in periodic supervision.

Conclusion

The findings provide valuable insights into the characteristics and practices of OD teams globally, highlighting the need for increased training opportunities, supervision, and research engagement. Future research should follow the development of OD implementation over time, complement self-assessment with rigorous observations and external evaluations, focus on involving different stakeholders in the OD-self-assessment and investigate the long-term outcomes of OD in different contexts.