bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel approach using automated target enrichment enables culture-independent accurate whole-genome sequencing of Neisseria gonorrhoeae directly from clinical urogenital and extragenital specimens
Authors: Golparian Daniel , Rapp Ellionor , Hasmats Johanna , Unemo Magnus
Published: December 2024

Objectives

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is compromising gonorrhoea treatment, and enhanced N. gonorrhoeae AMR and genome-based epidemiological surveillance is imperative. Molecular tests are replacing N. gonorrhoeae culture internationally, excluding possibilities to perform WGS. We describe and evaluate a novel approach using a custom SureSelectXTHS Target-Enrichment probe panel automated on the Magnis NGS Prep System and Illumina sequencing to generate accurate N. gonorrhoeae genomes directly from clinical urogenital and extragenital specimens.

Methods

One hundred thirteen clinical N. gonorrhoeae-positive APTIMA Combo 2 (AC2) specimens (with 89 linked N. gonorrhoeae isolates) were included. DNA was extracted using QIAsymphony DSP Virus/Pathogen kit. Amplisens multiplex RT–PCR assay (AM-PCR) identified 105 (92.9%) of the AC2 specimens as N. gonorrhoeae positive, which were further examined. Sequence libraries for AC2 specimens were prepared on the Magnis NGS Prep System using the Magnis SureSelectXTHS Reagent kit for Illumina paired-end platforms. Paired-end sequencing was performed on Illumina platforms.

Results

Seventy-four of the 105 (70.5%) AC2 samples remained N. gonorrhoeae positive with a cycle threshold <20 in the AM-PCR and subjected to SureSelectXTHS target enrichment and subsequently Illumina WGS. Seventy-two (97.3%) of all target-enriched specimens were successfully genome-sequenced. All linked AC2 specimens and N. gonorrhoeae isolates from the same anatomical site had identical AMR determinants and molecular epidemiological sequence types.

Conclusions

We show that custom SureSelectXTHS target enrichment automated on the Magnis NGS Prep System, followed by Illumina sequencing, enables culture-independent genome-based surveillance of N. gonorrhoeae AMR and molecular epidemiology. This novel methodological advancement provides an efficient and accurate WGS of N. gonorrhoeae directly from clinical urogenital and extragenital NAAT specimens.
Genetics of recombination rate variation within and between species
Authors: Payseur Bret A
Published: December 2024

Recombination diversifies the genomes of offspring, influences the evolutionary dynamics of populations, and ensures that chromosomes segregate properly during meiosis. Individuals recombine at different rates, but observed levels of variation in recombination rate remain mostly unexplained. Genetic dissection of differences in recombination rate within and between species provides a powerful framework for understanding how this trait evolves. In this Perspective, I amalgamate published findings from genetic studies of variation in the genome-wide number of crossovers within and between species, and I use exploratory analyses to identify preliminary patterns. The narrow-sense heritability of crossover count is consistently low, indicating limited resemblance among relatives and predicting a weak response to short-term selection. Variants associated with crossover number within populations span the range of minor allele frequency (MAF). The size of the additive effect of recombination-associated variants, along with a negative correlation between this effect and MAF, raises the prospect that mutations inducing phenotypic shifts larger than a few crossovers are deleterious, though the contributions of methodological biases to these patterns deserve investigation. Quantitative trait loci that contribute to differences between populations or species alter crossover number in both directions, a pattern inconsistent with selection toward a constant optimum for this trait. Building on this characterization of genetic variation in crossover number within and between species, I describe fruitful avenues for future research. Better integrating recombination rate into quantitative genetics will reveal the balance of evolutionary forces responsible for genetic variation in this trait that shapes inheritance.
A chromosome-level genome of the giant vinegaroon Mastigoproctus giganteus exhibits the signature of pre-Silurian whole genome duplication
Authors: Kulkarni Siddharth S , Klementz Benjamin C , Sharma Prashant P
Published: December 2024

Within the arachnids, chromosome-level genome assemblies have greatly accelerated the understanding of gene family evolution and developmental genomics in key groups, such as spiders (Araneae), mites and ticks (Acariformes and Parasitiformes). Among other poorly studied arachnid orders that lack genome assemblies altogether are members of the clade Pedipalpi, which is comprised of three orders that form the sister group of spiders and diverged over 400 Mya. We close this gap by generating the first chromosome-level assembly from a single specimen of the vinegaroon Mastigoproctus giganteus (Uropygi). We show that this highly complete genome retains plesiomorphic conditions for many gene families that have undergone lineage-specific derivations within the more diverse spiders. Consistent with the phylogenetic position of Uropygi, macrosynteny in the M. giganteus genome substantiates the signature of an ancient whole genome duplication.
Role of radiation emergency medicine: historical view—a perspective on the past, present, and future
Authors: Akashi Makoto
Published: December 2024

The more science progresses, the more life and society change. Medicine also changes with the times and the culture. This is also true for radiation emergency medicine, which includes dose-assessment leading to diagnosis, treatment, medical follow-up and prognosis of persons who have developed acute injury or illness due to radioactive contamination or radiation exposure. Before the report of X-rays by Roentgen, there was evidence that X-rays had been emitted from the electrically excited Crookes tube and that skin injury had been caused by the X-rays. Thus, the history of radiation and its exposure started before Roentgen. During the early stage of radiation use, people were simply exposed to radiation but were unaware of any danger. Radioactive materials were found soon after Roentgen’s report, and contamination with these materials occurred. Together with the development of science and technology, sophisticated radiation devices were produced, and the use and application of radiation became much enhanced. New radionuclides were found one after another, leading to identification of different qualities of radiation. Development of nuclear physics allowed people to artificially produce radionuclides and to construct a nuclear reactor. After World War II, nuclear power plants were constructed, and related facilities such as nuclear fuel processing, reprocessing and spent fuel storage facilities were built. If radiation accidents or events occur at such facilities, radiation exposure with thermal or chemical burns could occur. Together with the expansion of globalism in the world and division in the society, there are now increasing concerns regarding the malicious usage of radiation by radiological dispersal devices (RDDs) including a dirty bomb. Upon detonation of RDDs, blast and thermal injuries with radiation exposure could be caused. In the present society, the natures of exposure to radiation and contamination with radioactive materials have become much more complicated. Not even mentioning the atomic bomb, the detonation of RDDs also necessitates scenarios of medical responses to complicated injuries and the involvement of numbers of people. This article looks back at the history of radiation and addresses the medical responses to radiation injuries that change with the times.
Estimating prevalence of opiate and crack cocaine use and injecting in England using mixed-effects capture–recapture models
Authors: Djennad Abdelmajid , Harris Ross J , Presanis Anne M , Jahr Stefan , Charlett Andre , De Angelis Daniela
Published: December 2024

Multiple social and health problems are associated with opiate and crack cocaine use and injecting, but the prevalence of these behaviours is unknown. We linked three sources of administrative data on individuals engaging in opiate and/or crack cocaine use (OCU) community treatment; arrests, prison, or probation; and drug-related deaths. We used probabilistic linkage to increase the number of matching records and capture-recapture analysis to estimate the unknown number of individuals not observed in any source. We fitted random effects models to data stratified by source, local authority (LA) area, age, sex, drug type, and injecting. Two-way interactions between sources and explanatory variables were included as fixed effects. We included random effects at the LA level, with random intercepts and random coefficients. The total count of opiate and/ or crack cocaine use in the financial year 2018/19 was estimated at 336,531 [95% confidence interval (CI): 311,932-360,845], corresponding to 9.44 (95% CI: 8.75-10.12) per 1,000 population in England. Three-quarters were men, and the estimate of people currently injecting drugs was 67,715 (95% CI: 64,769-70,526). Our study used random effects models to borrow strength across local authorities and produce robust prevalence estimates of OCU for England
Unveiling the virulence mechanism of Leptosphaeria maculans in the Brassica napus interaction: the key role of sirodesmin PL in the induction of cell death
Authors: Pombo Marina A , Rosli Hernan G , Maiale Santiago , Elliott Candace , Stieben Micaela E , Romero Fernando M , Garriz Andrés , Ruiz Oscar A , Idnurm Alexander , Rossi Franco R
Published: December 2024

Leptosphaeria maculans is the causal agent of blackleg disease in Brassica napus, leading to substantial yield losses. Sirodesmin PL, the principal toxin produced by L. maculans, has been implicated in the infection process in plants. However, the precise molecular and physiological mechanisms governing its effects remain elusive. This study investigates the changes induced by sirodesmin PL at the transcriptomic, physiological, and morphological levels in B. napus cotyledons. Sirodesmin PL treatment up-regulated genes associated with plant defense processes, including response to chitin, sulfur compound biosynthesis, toxin metabolism, oxidative stress response, and jasmonic acid/ethylene synthesis and signaling. Validation of these transcriptomic changes is evidenced by several typical defense response processes, such as the accumulation of reactive oxygen species (ROS) and callose deposition. Concomitantly, oxidized sirodesmin PL induced concentration- and exposure duration-dependent cell death. This cellular death is likely to be attributed to diminished activity of PSII and reduced number of chloroplasts per cell. In agreement, a down-regulation of genes associated with the photosynthesis process is observed following sirodesmin PL treatment. Thus, it is plausible that L. maculans exploits sirodesmin PL as a virulence factor to instigate cell death in B. napus during its necrotrophic stage, favoring the infection process.
The homeodomain leucine zipper protein RhHB22 promotes petal senescence by repressing ascorbic acid biosynthesis in rose
Authors: Li Ping , Qiu Yuexuan , Wang Rui , Zhang Bingjie , Ma Yanxing , Sun Xiaoming , Gao Junping , Jiang Yunhe
Published: December 2024

Premature petal senescence dramatically reduces flower quality and value. Ethylene and reactive oxygen species (ROS) are key players in accelerating rose petal senescence, but the molecular mechanism by which ethylene antagonizes ROS scavenging is not well understood. Here, we showed that ethylene reduces ascorbic acid (AsA) production, leading to the accumulation of ROS and hastening petal senescence. Ethylene treatment suppressed the expression of GDP-l-galactose phosphorylase 1 (RhGGP1), encoding the rate-controlling enzyme in AsA biosynthesis. A HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP) II transcription factor, RhHB22, directly bound to the promoter of RhGGP1 and inhibited its transcription. RhHB22 is induced by ethylene, and silencing of RhHB22 increased RhGGP1 expression and AsA production, resulting in reduced H2O2 accumulation and delayed petal senescence. Additionally, the delayed petal senescence symptoms of RhHB22-silenced plants were suppressed by silencing RhGGP1. Moreover, the expression of RhGGP1, which is suppressed by ethylene in wild-type petals, was significantly compromised in RhHB22-silenced petals. These findings uncover the transcriptional regulatory mechanism by which ethylene promotes ROS accumulation and petal senescence by inhibiting AsA biosynthesis, enhance our understanding of ethylene-induced petal senescence, and provide novel insights for improving the longevity of cut flowers.
Use of a small molecule microarray screen to identify inhibitors of the catalytic RNA subunit of Methanobrevibacter smithii RNase P
Authors: Sidharthan Vaishnavi , Sibley Christopher D , Dunne-Dombrink Kara , Yang Mo , Zahurancik Walter J , Balaratnam Sumirtha , Wilburn Damien B , Schneekloth John S , Gopalan Venkat
Published: December 2024

Despite interest in developing therapeutics that leverage binding pockets in structured RNAs—whose dysregulation leads to diseases—such drug discovery efforts are limited. Here, we have used a small molecule microarray (SMM) screen to find inhibitors of a large ribozyme: the Methanobrevibacter smithii RNase P RNA (Msm RPR, ∼300 nt). The ribonucleoprotein form of RNase P, which catalyzes the 5′-maturation of precursor tRNAs, is a suitable drug target as it is essential, structurally diverse across life domains, and present in low copy. From an SMM screen of 7,300 compounds followed by selectivity profiling, we identified 48 hits that bound specifically to the Msm RPR—the catalytic subunit in Msm (archaeal) RNase P. When we tested these hits in precursor-tRNA cleavage assays, we discovered that the drug-like M1, a diaryl-piperidine, inhibits Msm RPR (KI, 17 ± 1 μM) but not a structurally related archaeal RPR, and binds to Msm RPR with a KD(app) of 8 ± 3 μM. Structure–activity relationship analyses performed with synthesized analogs pinpointed groups in M1 that are important for its ability to inhibit Msm RPR. Overall, the SMM method offers prospects for advancing RNA druggability by identifying new privileged scaffolds/chemotypes that bind large, structured RNAs.
Rubisco packaging and stoichiometric composition of the native β-carboxysome in Synechococcus elongatus PCC7942
Authors: Sun Yaqi , Sheng Yuewen , Ni Tao , Ge Xingwu , Sarsby Joscelyn , Brownridge Philip J , Li Kang , Hardenbrook Nathan , Dykes Gregory F , Rockliffe Nichola , Eyers Claire E , Zhang Peijun , Liu Lu-Ning
Published: December 2024

Carboxysomes are anabolic bacterial microcompartments that play an essential role in CO2 fixation in cyanobacteria. This self-assembling proteinaceous organelle uses a polyhedral shell constructed by hundreds of shell protein paralogs to encapsulate the key CO2-fixing enzymes Rubisco and carbonic anhydrase. Deciphering the precise arrangement and structural organization of Rubisco enzymes within carboxysomes is crucial for understanding carboxysome formation and overall functionality. Here, we employed cryoelectron tomography and subtomogram averaging to delineate the 3D packaging of Rubiscos within β-carboxysomes in the freshwater cyanobacterium Synechococcus elongatus PCC7942 grown under low light. Our results revealed that Rubiscos are arranged in multiple concentric layers parallel to the shell within the β-carboxysome lumen. We also detected Rubisco binding with the scaffolding protein CcmM in β-carboxysomes, which is instrumental for Rubisco encapsulation and β-carboxysome assembly. Using Quantification conCATamer-based quantitative MS, we determined the absolute stoichiometric composition of the entire β-carboxysome. This study provides insights into the assembly principles and structural variation of β-carboxysomes, which will aid in the rational design and repurposing of carboxysome nanostructures for diverse bioengineering applications.
Burnout among medical residents: key drivers and practical mitigating strategies
Authors: Ng Isaac K S , Tham Sarah Z L , Chong Kar Mun , Goh Wilson G W , Thong Christopher , Teo Kevin Soon Hwee
Published: December 2024

Burnout is a prevalent phenomenon in medicine, affecting >50% of physicians and up to 60% of medical residents. This has negative consequences for both doctors’ mental health and job satisfaction as well as patient care quality. While numerous studies have explored the causes, psychological effects, and workplace solutions, we aim to practicalize the issue from the perspectives of residents by discussing three key drivers of burnout and offering actionable, multipronged strategies that may be able to tackle these root causes effectively. From review of relevant literature and personal reflections/experiences, we identified three key factors that contribute to resident burnout, namely, (i) inherent physician attributes, (ii) mismatched expectations of the medical profession, and (iii) stressful nature of clinical work and residency training for junior physicians. We offer practical strategies that can be implemented by various stakeholders in a concerted manner to target these three areas, namely, to inculcate and foster accurate perception of the medical profession at the outset, develop psychological strength/resilience among medical residents, and make practical improvements to working and training environments.
Incorporating computer vision on smart phone photographs into screening for inflammatory arthritis: results from an Indian patient cohort
Authors: Phatak Sanat , Saptarshi Ruchil , Sharma Vanshaj , Shah Rohan , Zanwar Abhishek , Hegde Pratiksha , Chakraborty Somashree , Goel Pranay
Published: December 2024

Objectives

Convolutional neural networks (CNNs) are increasingly used to classify medical images, but few studies utilize smartphone photographs. The objective of this study was to assess CNNs for differentiating patients from controls and detecting joint inflammation.

Methods

We included consecutive patients with early inflammatory arthritis and healthy controls, all examined by a rheumatologist (15% by two). Standardized hand photographs of the hands were taken, anonymized and cropped around joints. Pre-trained CNN models were fine-tuned on our dataset (80% training; 20% test set). We used an Inception-ResNet-v2 backbone CNN modified for two class outputs (patient vs control) on uncropped photos. Separate Inception-ResNet-v2 CNNs were trained on cropped photos of middle finger proximal interphalangeal (MFPIP), index finger proximal interphalangeal (IFPIP) and wrist. We report accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC).

Results

We analysed 800 hands from 200 controls (mean age 37.8 years) and 200 patients (mean age 49 years). Two rheumatologists showed 0.89 concordance. The wrist was commonly involved (173/400) followed by the MFPIP (134) and IFPIP (128). The screening CNN achieved 99% accuracy and specificity and 98% sensitivity in predicting a patient compared with controls. Joint-specific CNN accuracy, sensitivity, specificity and AUC were as follows: wrist (75%, 92%, 72% and 0.86, respectively), IFPIP (73%, 89%, 72% and 0.88, respectively) and MFPIP (71%, 91%, 70% and 0.87, respectively).

Conclusion

Computer vision distinguishes patients and controls using smartphone photographs, showing promise as a screening tool. Future research will focus on validating findings in diverse populations and other joints and integrating this technology into clinical workflows.
Implementing an artificial intelligence system into a diabetic eye screening programme in Tanzania
Authors: Cleland Charles R , Makupa William U , Shilio Bernadetha R , Rwiza Justus , Macleod David , Bascaran Covadonga , Burton Matthew J
Published: December 2024

Tanzania has the highest age-adjusted prevalence of diabetes in sub-Saharan Africa. Diabetic retinopathy, a common complication, is a significant cause of vision loss; but with effective screening and treatment this often can be prevented. However, with very few specialist eye care staff in Tanzania this is a major challenge. Artificial intelligence (AI) systems, which automate clinical decision making and therefore task-shift away from specialist staff, could contribute to improved diabetic retinopathy screening services in low-resource settings. This article describes our experiences of selecting, procuring and implementing an AI system into a regional diabetic eye screening programme in northern Tanzania.
A hidden finch from the Galapagos Islands: a genetically and morphologically distinctive woodpecker finch from San Cristobal Island
Authors: Lawson Lucinda P , Nemeth Erwin , Dvorak Michael , Cunninghame Francesca , Fessl Birgit , Mueller Jakob C , Mosquera Denis , Wendelin Beate , Petren Kenneth
Published: December 2024

The Galapagos finches represent a rapid radiation of birds across the remote oceanic archipelago that vary morphologically, behaviourally, and genetically. The level of diversity and rapid rate of speciation have created taxonomic difficulties in resolving phylogenetic relationships. While much of the phylogeny has recently been clarified with modern genomic methods, some of the diversity has been overlooked by under-sampling across islands within presumed species. The woodpecker finch, Camarhynchus pallidus Sclater and Salvin, 1870, represents one such lineage, as all three recognized subspecies have never been fully phylogenetically assessed in regard to their species’ status and relationship with their close sister-species, the mangrove finch (C. heliobates; Snodgrass and Heller 1901). Using genetic and genomic tools, along with morphological analyses, we show that the San Cristobal woodpecker finch (C. p. striatipecta; Swarth 1931) is genetically distinct and paraphyletic with the mangrove finch, compared to all other woodpecker finch subspecies. Given these results we propose that the San Cristobal woodpecker finch be prioritized for further research, as our results hint that it should be given full species’ status as Camarhynchus striatipecta Swarth, 1931.
Effects of Botulinum Toxin Type A Treatment on Clinical and Biophysical Parameters in Patients With Erythematotelangiectatic Rosacea: A Prospective, Randomized, Controlled, Double-Blind Study
Authors: Dağtaş Buğra Burç , Erdem Ozan , Güneç Tuğba İlter , Avcı Elif Bal , Manav Vildan , Koku Aksu Ayşe Esra
Published: December 2024

BACKGROUND

Erythematotelangiectatic rosacea (ETR) lacks a gold-standard treatment. Recent studies show that intradermal Botulinum Toxin-A (BoNT-A) is effective for erythema, though objective data are limited.

OBJECTIVE

This study aims to evaluate the efficacy and tolerability of intradermal BoNT-A in patients with ETR.

METHODS

In this randomized, double-blind, split-face study, 30 patients were enrolled. One side of the face received 15 units of BoNT-A, reconstituted in 10 mL of saline, while the control side received saline injections. Assessments were made at baseline and 1-month posttreatment. Clinician's Erythema Assessment (CEA) scale and Patient Self-Assessment (PSA) scores were recorded. Erythema and Melanin Index measurements using a Mexameter. Background erythema was assessed through dermatoscopy, while vascular structure and density were evaluated using Investigative Global Assessment (IGA) scores through videocapillaroscopy.

RESULTS

The BoNT-A-treated side demonstrated significant reductions in CEA scores, Erythema Index, and dermatoscopic background erythema, while no significant changes were observed on the saline control side. IGA scores indicated a significant response to treatment on the BoNT-A side. Patient Self-Assessment scores improved on both sides. No serious adverse events requiring hospitalization were reported.

CONCLUSION

Intradermal BoNT-A effectively reduces erythema and vascular density in patients with ETR and is well-tolerated.
Greenhouse gas emissions due to inhalation anaesthetics in the Netherlands, usage data and a survey of preferences among Dutch anaesthesiologists
Authors: Friedericy Herman J. , Venema Pascale A.H.T. , Lockyer Jessica F. , Kweekel Dinemarie M. , van der Eijk Anne C. , Jansen Frank Willem , Sarton Elise Y.
Published: December 2024

BACKGROUND

Anaesthetic gases are an important source of greenhouse gas emissions from operating theatres and can attribute significantly to the carbon footprint of a nation's healthcare system.

OBJECTIVE

To estimate the magnitude of the climate impact of inhaled anaesthetics in the Netherlands. Furthermore, the goal was to assess the preferences of Dutch anaesthesiologists for anaesthesia techniques, and to explore opportunities for reducing greenhouse gas emissions due to anaesthesia practice.

DESIGN

A 2019 bottom-up purchase analysis of inhalation anaesthetics used in all of the Dutch hospitals was executed and an online survey was conducted among Dutch anaesthesiologists regarding their preferences for anaesthetic agents.

RESULTS

Purchasing quantities of volatile anaesthetic agents were obtained from 61 of the 69 hospital organisations in the Netherlands (response rate 88.4%). A total of 12.2 kilotons CO2 equivalent (0.07% of the Dutch healthcare system) was emitted due to inhalation anaesthetics in the Netherlands in 2019. The volume of the in 2019 purchased inhalation volatile anaesthetics was 9.178 l of sevoflurane (93.4%), 404 l of desflurane (4.1%) and 245 l of isoflurane (2.5%). The survey in which 182 anaesthesiologists participated demonstrated that propofol was the first drug of choice of 70% of respondents, desflurane was available in 16% of Dutch hospitals and 83% of anaesthesiologists answered never using desflurane. Nitrous oxide was not used by 63% of respondents, the remaining 27% reported using nitrous oxide only in less than 5% of their cases.

CONCLUSION

The relatively low emission of greenhouse gases due to inhalation anaesthetics in Dutch healthcare compared to other countries can be explained by the limited use of nitrous oxide and desflurane by Dutch anaesthesiologists and their strong preference for intravenously administered propofol as an anaesthetic.
Mortality after concurrent treatment with gabapentin and opioids in older adults with spine diagnoses
Authors: Gold Laura S. , Heagerty Patrick J. , Hansen Ryan N. , Friedly Janna L. , Johnston Sandra K. , Deyo Richard A. , Curatolo Michele , Turner Judith A. , Rundell Sean D. , Wysham Katherine , Jarvik Jeffrey G. , Suri Pradeep
Published: December 2024

Given the negative impact of opioid use on population health, prescriptions for alternative pain-relieving medications, including gabapentin, have increased. We wanted to determine whether people who filled gabapentin and opioid prescriptions concurrently (“gabapentin + opioids”) had greater mortality than those who filled an active control medication (tricyclic antidepressants [TCAs] or duloxetine) and opioids concurrently (“TCAs/duloxetine + opioids”). In this population-based, propensity score-matched cohort study, we identified Medicare beneficiaries with spine-related diagnoses from 2017 to 2019. We compared people treated with gabapentin + opioids (n = 67,133) to people treated with TCAs/duloxetine + opioids (n = 67,133) who were matched on demographic and clinical factors. The primary outcome was mortality at any time, and a secondary outcome was occurrence of a major medical complication at any time. Among 134,266 participants (median age 73.4 years; 66.7% female), 2360 died before the end of follow-up. No difference in mortality was observed between groups (adjusted hazard ratio and 95% confidence interval for gabapentin + opioids 0.98 [0.90-1.06]; P = 0.63). However, people treated with gabapentin + opioids were at slightly increased risk of a major medical complication (1.02 [1.00-1.04]; P = 0.03) compared to those treated with TCAs/duloxetine + opioids. Results were similar in analyses (1) restricted to ≤30-day follow-up and (2) that required ≥2 fills of each prescription. When treating pain in older adults taking opioids, the addition of gabapentin did not increase mortality risk relative to addition of TCAs or duloxetine.
Signatures of chronic pain in multiple sclerosis: a machine learning approach to investigate trigeminal neuralgia
Authors: Latypov Timur H. , Wolfensohn Abigail , Yakubov Rose , Li Jerry , Srisaikaew Patcharaporn , Jörgens Daniel , Jones Ashley , Colak Errol , Mikulis David , Rudzicz Frank , Oh Jiwon , Hodaie Mojgan
Published: December 2024

Chronic pain is a pervasive, disabling, and understudied feature of multiple sclerosis (MS), a progressive demyelinating and neurodegenerative disease. Current focus on motor components of MS disability combined with difficulties assessing pain symptoms present a challenge for the evaluation and management of pain in MS, highlighting the need for novel methods of assessment of neural signatures of chronic pain in MS. We investigate chronic pain in MS using MS-related trigeminal neuralgia (MS-TN) as a model condition focusing on gray matter structures as predictors of chronic pain. T1 imaging data from people with MS (n = 75) and MS-TN (n = 77) using machine learning (ML) was analyzed to derive imaging predictors at the level of cortex and subcortical gray matter. The ML classifier compared imaging metrics of patients with MS and MS-TN and distinguished between these conditions with 93.4% individual average testing accuracy. Structures within default-mode, somatomotor, salience, and visual networks (including hippocampus, primary somatosensory cortex, occipital cortex, and thalamic subnuclei) were identified as significant imaging predictors of trigeminal neuralgia pain. Our results emphasize the multifaceted nature of chronic pain and demonstrate the utility of imaging and ML in assessing and understanding MS-TN with greater objectivity.
Research progress of brain-computer interface applied in the rehabilitation of dysarthria and speech function in amyotrophic lateral sclerosis
Authors: Liu Lizhu , Zeng Xianwei
Published: December 2024

With the development of brain science research, artificial intelligence technologies such as brain-computer interface (BCI) have begun to be applied in the medical field. People with advanced amyotrophic lateral sclerosis (ALS) lose voluntary control, including the ability to communicate. For ALS patients, BCI research focuses on communication. BCI technology can be used as a communication tool. It records and extracts features of brain signals and translates these features into commands that can be replaced, restored, enhanced, supplemented, or improved by the central nervous system. Some BCIs have been shown to have potential spillover for ALS patients. However, there are still some challenges that need to be addressed before BCI can be clinically useful.
Baseline and early dynamic changes in inflammatory and nutritional status can predict survival in patients with advanced biliary tract carcinoma receiving immunotherapy: A retrospective cohort study
Authors: Shen Hao-Yang , Wang Fang , Zhang Jia-Guang , Tian Yi-Tong , Jin Ke , Zhang Xin-Yi , Ji Lian-Hua , Ding Yu-Ting , Qian Hao , Ma Ling , Chen Xiao-Feng , Xu Lu
Published: December 2024

Background

Inflammatory and nutritional indicators are established prognostic factors in patients with various types of solid tumors. However, it remains unclear whether differences in the baseline and early dynamic changes in these factors can predict the prognosis of immunotherapy in patients with advanced biliary tract carcinoma (aBTC).

Methods

Data were retrospectively collected from 74 consecutive patients who were diagnosed with aBTC and received immunotherapy. Peripheral blood cell counts and other laboratory tests were performed at baseline and after two cycles of immunotherapy. The skeletal muscle index was measured using computed tomography/magnetic resonance imaging scans. Analyses of the relationship between clinicopathological characteristics and survival outcomes were conducted using Kaplan-Meier curves and Cox regression models.

Results

Seventy-four patients were enrolled in the study, with 42 (56.8%) being male. The median age at diagnosis for all participants was 61 years (range, 35–77 years). In the univariate analysis, six baseline indices were associated with survival, namely, lactate dehydrogenase (LDH), carbohydrate antigen 199, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, Prognostic Nutritional Index, and Controlling Nutritional Status score. In the multivariable analysis, an elevated baseline NLR (HR: 3.363, 95% CI: 1.600–7.070, P = 0.001) and elevated baseline LDH (HR: 2.030, 95% CI: 1.122–3.670, P = 0.019) were independent risk factors for a shorter overall survival. Sarcopenia was not correlated with the overall survival (P > 0.05). A persistently high NLR, platelet-to-lymphocyte ratio, and Controlling Nutritional Status score and low Prognostic Nutritional Index indicated a worse prognosis.

Conclusions

Elevated baseline NLR and LDH values are independent negative prognostic factors in patients with aBTC receiving immunotherapy. Patients with persistently high inflammation and poor nutritional status experience a poorer prognosis.
Bibliometric analysis of global research on vitamins and cancer between 2003 and 2022
Authors: Wang Wen , Ye Xiangming , Wang Sisi
Published: December 2024

Background:

Vitamins are essential nutrients that play an indispensable role in maintaining the vital functions of the human body. A growing number of studies have shown a link between vitamins and cancer. However, there is no systematic review and bibliometric analysis in this field. This study aims to summarize the hotspots and emerging research topics in this field of vitamins and cancer research.

Methods:

Articles on the topic of vitamins and cancer published between 2003 and 2022 were retrieved from the Web of Science core collection database (WOSCC) on May 1, 2023. Subsequently, we conducted VOSviewer and CiteSpace to examine the annual output distribution, countries/regions, institutions, journals, authors, co-cited references, and keywords.

Results:

A total of 3166 publications were extracted using a timespan of 2003 to 2022. The number of publications has grown rapidly over the past 20 years. Most publications were from the United States; Harvard University was the most active institutions; Giovannucci stood out among authors with the highest number of publications, citations and H-index; Cancer Epidem Biomar published the most papers in this field; the highest cited reference was published in Nat Rev Cancer, authored by Feldman in 2014. Breast cancer was the most common type of cancer, while vitamin D was a research hotspot in this field. Oxidative stress may be the primary anticancer mechanism of vitamins, while also involving epithelial-mesenchymal transition, apoptosis, polymorphism, and calcium metabolism. “nanoparticle” may be the new focus of attention in the next few years.

Conclusion:

This study presented an overview of the major research directions of vitamins and cancer by bibliometric methods over the past 2 decades. The results could reveal the research trends and the hotspots in the field and provide helpful information for clinical treatments of cancer.
Whether perceived limb heaviness affects return to work among patients with ischemic stroke
Authors: Chen Yuanyuan , Yang Hongyan , Chen Yanqin , Wei Hui , Lan Meijuan
Published: December 2024

This study aims to explore the relationship between perceived limb heaviness and return to work (RTW) among ischemic stroke patients. We retrospectively reviewed the data of consecutive participants recruited in the CIRCLE study. Perceived limb heaviness was gathered from self-reported by 1-year follow-up. The chi-square test and logistic regression analysis were used to analyze the independent risk factors of RTW. A total of 209 participants completed the study. The participants were predominately 81.3% male, with a mean age of 51.24 ± 9.09 years. In total, 79 participants (37.8%) had returned to work 12 months after the stroke, 36 (17.2%) felt limb heaviness, and 67.9% had a son or 2 sons. The participants who had not RTW were on contemplation status, and those who had RTW were on proactive maintenance status. Logistic regression analysis showed that participants with 2 sons were independently associated with an increased chance of RTW (P = .016, odds ratio [OR] = 3.990). Participants who had perceived limb heaviness were independently associated with a low rate of RTW compared with no perceived limb heaviness (P = .009, OR = 0.235). This research finds that participants experiencing limb heaviness might lower the rate of RTW after 12 months. The other interesting finding is that participants with 2 sons might have a higher rate of RTW.
Laboratory biosafety: A visual analysis in the web of science database from 2000 to 2022: A review
Authors: Qi Sunyun , Chen Siyuan , Witte Dries De , Molenberghs Geert , Zhang Qifeng , Gu Hua , Gao Yanchao
Published: December 2024

To conduct a visual analysis of institutional publications, individual publications and publication keywords in the field of laboratory biosafety using the Web of Science database from 2000 to 2022.VOSviewer 1.6.18 was used to study the relation between paper authors, and CiteSpace 6.1.R6 was used to visualize the collaboration between the paper institutions, the paper keywords and the timeline. The main research institutions included the Centers for Disease Control and Prevention (USA), and the University of Chinese Academy of Sciences (China). The collaboration between the research institutions was limited and dispersed. Each of the main study teams is led by Feldmann Heinz, Peter B. Jahrling, Roger Hewson, and Li Na. Infection, identification, and outbreak are the keywords that appear more often and are also of higher importance in publications. The citation burst of keywords varies over time: outbreak, resistance, and polymerase chain reaction from 2004 to 2012; gene, cells, and Ebola from 2013 to 2017; and spread, safety, coronavirus, and African swine fever from 2018 to 2022. The centralization of research teams and individuals in laboratory biosafety is not conducive to the growth of disciplinary diversity. These publication keywords are mainly align with significant social events, scientific and technological development trends, and national strategic needs. This paper advocates for a more balanced allocation of resources and collaboration opportunities to foster diversity and address emerging challenges in the field of laboratory biosafety.
Epimedium applied in the clinical treatment of osteoporosis patients with periodontitis
Authors: Guo Ying , Ge Xu , Wang Wei , Wang Rongrong , Chen Qianmin , Wang Hong
Published: December 2024

Osteoporosis and periodontitis, prevalent in middle-aged and elderly populations, share common features of bone loss and chronic inflammation. This study explores the hypothesis that Epimedium, known for its bone-strengthening properties, may enhance the effectiveness of conventional osteoporosis treatment in patients with coexisting periodontitis. This retrospective study analyzed clinical data from 120 patients with osteoporosis and periodontitis, divided into 2 groups. The control group received calcium carbonate, vitamin D, and zoledronic acid (CC + VD + ZA) therapy, while the observation group received additional Epimedium flavonoid treatment. Outcomes assessed included changes in bone mineral density (BMD), bone metabolism markers (β-CTx, N-MID, CT, ALP), periodontal indices (PD, AL, SBI, PLI), and inflammatory markers in gingival crevicular fluid (GCF) before and 6 months posttreatment. Compared to the control group, the observation group showed significantly greater increases in lumbar spine and proximal femur BMD and reductions in BM markers (P < .05). Periodontal health metrics (PD, AL, SBI, PLI) and GCF inflammatory markers (TNF-α, IL-1β, IL-6, IL-8, hs-CRP, ICAM-1, HMGB1, PGE2) were markedly improved in the observation group, correlating with enhanced total effective rates (TER) for osteoporosis (95.0%) and periodontitis (91.7%) and a reduced adverse event rate (AER). Epimedium shows promise as an adjunctive therapy in patients with osteoporosis and periodontitis, contributing to improved BMD, reduced inflammation, and enhanced periodontal health, suggesting its potential for broader clinical application in managing these coexisting conditions.
Complex pancreaticobiliary maljunction diagnosed by endoscopic ultrasound: A case report
Authors: Xu Wen , Lv Yang , Zhu Ying , Zhang Yingchun , Gong Wei , Cui Xiaobing
Published: December 2024

Rationale:

This case report aims to enhance understanding of pancreatobiliary maljunction (PBM) and promote more proactive treatment.

Patient concerns:

The patient, a 24-year-old Chinese female, was admitted to the hospital on April 7, 2020, due to “recurrent abdominal pain for over 2 years, with a recent episode accompanied by nausea and vomiting for 1 day.” She had a previous history of gallstones.

Diagnoses:

The initial diagnosis upon admission was biliary acute pancreatitis. During the emergency endoscopic retrograde cholangiopancreatography (ERCP) procedure, anatomical abnormalities were discovered. Intraoperative endoscopic ultrasonography led to a diagnosis of complex PBM (JSPBM, type D) + choledochal cyst (Todani, Ic) + incomplete pancreatic divisum + early chronic pancreatitis. These diagnoses were confirmed by postoperative magnetic resonance cholangiopancreatography.

Interventions:

After multiple conservative treatments such as ERCP with accessory pancreatic duct stent placement, the patient underwent surgical treatment in April 2021, which included “laparoscopic left hemihepatectomy + choledochal cyst excision + cholecystectomy + hepatic portal cholangioplasty.”

Outcomes:

The patient has not experienced any abdominal pain since the surgery and is currently under regular follow-up.

Lessons:

Endoscopic ultrasound is effective for the diagnoses of complex PBM and incomplete pancreatic divisum. ERCP with pancreatic duct stent placement and surgical procedure is reliable for relieving the patient’s symptoms.
A single center retrospective study of vNOTES hysterectomy, laparoscopic hysterectomy and vaginal hysterectomy operations
Authors: Mollahüseyinoğlu Küllaç Fatmanur , Özdemir Ayşe Zehra , Yildiz Çağlanur
Published: December 2024

In our study, we aimed to retrospectively compare vNOTES hysterectomy, a new method, with a vaginal hysterectomy (VH) and total laparoscopic hysterectomy (TLH). Our study included 186 hysterectomy cases (62 vNOTES hysterectomy, 62 VH, and 62 TLH) with benign indications diagnosed between 2021 and 2022. Our study is a retrospective and single-center study. Three surgical techniques were evaluated comparatively according to demographic characteristics and surgical results. The least hemoglobin (Hb) decline and the longest mean operation time were observed in the vNOTES hysterectomy group. When discharge times were compared, it was observed that the vNOTES hysterectomy group was discharged significantly shorter than the TLH group (P: .022 < .05). The lowest 6th-hour pain score of 1.53 was observed in the vNOTES hysterectomy group. History of pelvic surgery and cesarean section were higher in the vNOTES hysterectomy group than in the VH group. Also, oophorectomy and salpingectomy rates were higher in the vNOTES hysterectomy group than in the VH group. When intraoperative complications were evaluated, bladder perforation was encountered in one vNOTES hysterectomy and two VH operations, and bleeding was observed in one VH operation. The VH group was the least costly operation compared to vNOTES hysterectomy and TLH (P: .003 < .05, P: .01 < .05). Aesthetic results can be achieved for patients by using the vaginal route. With all these results, we believe that vNOTES hysterectomy is a safe alternative to TLH and VH.
Successful management of immunotherapy-resistant respiratory failure in anti-mitochondrial M2 antibody-positive myositis by modified lung volume recruitment therapy: A case report
Authors: Takahashi Seiya , Inoue Hiroyasu , Amano Shizuki , Shinohara Takahiro , Mori Sara , Onizawa Kaho , Nabeshima Yoko , Komuro Hiroyasu , Yasumoto Taro , Mitsuhashi Rihito , Watanabe Daishi , Komaba Kazuki , Futamura Akinori , Nogawa Satoshi , Kinno Ryuta
Published: December 2024

Rationale:

Anti-mitochondrial antibodies (AMA) M2-positive myositis can lead to severe respiratory failure. Traditional immunotherapies sometimes fail to address respiratory failure. Herein, this CARE-compliant case report described a patient with AMA-M2-positive myositis who recovered from ventilation with tracheostomy owing to immunotherapy-resistant respiratory failure to spontaneous breathing after modified lung volume recruitment (mLVR) therapy.

Patient concerns:

A 60-year-old man experienced general fatigue and shortness of breath. The patient had a notable degree of proximal muscle weakness. Blood test results revealed hyperCKemia. The serum AMA-M2 antibody was positive. A muscle magnetic resonance imaging revealed diffuse abnormal hyperintensities in both lower limb muscles. Needle electromyography demonstrated fibrillation and positive sharp waves at rest with early recruitment, suggesting myogenic changes. Progressive muscle weakness and clinical findings fulfilled the criteria for definite idiopathic inflammatory myopathy. We diagnosed him with AMA-M2-positive myositis. Notably, his thoracic mobility was decreased, resulting in CO2 narcosis, requiring ventilation. Two courses of intravenous methylprednisolone for 3 days followed by oral prednisolone for myopathy. However, his respiratory function remained compromised, resulting in a tracheostomy.

Diagnoses:

We diagnosed him with severe immunotherapy-resistant respiratory failure due to AMA-positive myositis that required ventilation and tracheostomy.

Interventions:

To address respiratory failure, this patient underwent the mLVR therapy using the LIC TRAINER (LT). The pressure was adjusted by the operator using a bag-valve mask (BVM), starting at 1500 mL and increasing it up to a maximum of 2500 mL, while avoiding excessive airway pressure.

Outcomes:

Respiratory function was evaluated by objective measures using chest wall mobility, inspiratory capacity (IC), vital capacity (VC), tidal volume (TV), and subjective measures using the visual analogue scale (VAS). Both objective and subjective scales showed significant improvements. The patient was weaned off ventilation 48 days after the initiation of mLVR therapy.

Lessons:

The mLVR therapy is an effective respiratory rehabilitation for patients with weakened respiratory muscles or tracheostomy. It allows the intensity of treatment to be adjusted based on the patient’s symptoms, making it both highly effective and safe. This case suggests that mLVR therapy may be effective in treating severe, immunotherapy-resistant respiratory failure in AMA-positive myositis.