bluuebunny/crossref_metadata_2025 huggingface dataset:
5-Hydroxymethylcytosine (5-hmC) loss is a marker of malignancy in biliary neoplasms
Authors: Gonzalez-Mancera Miguel S , Siref Andrew , Kosari Kambiz , Nissen Nicholas , Gaddam Srinivas , Hendifar Andrew , Osipov Arsen , Waters Kevin , Hutchings Danielle , Guindi Maha , Larson Brent K
Published: February 2024

Objectives

Adenocarcinomas of the biliary tract frequently present diagnostic challenges because of their histologic overlap with benign and preinvasive lesions. The molecular profiles of biliary adenocarcinomas vary by anatomical location. Variations in IDH1/2, common in intrahepatic cholangiocarcinoma, can lead to defective production of 5-hydroxymethylcytosine (5-hmC). Limited ancillary studies are available for biliary adenocarcinomas, and loss of 5-hmC staining could serve as a helpful ancillary diagnostic tool for biliary tract malignancies.

Methods

We evaluated 93 cases—20 benign biliary lesions, 15 preinvasive biliary neoplasms, 46 invasive biliary carcinomas, and 12 pancreatic adenocarcinomas—for 5-hmC staining. Preoperative biopsies from 16 cases of biliary carcinoma were also stained. Sixteen nonneoplastic/reactive bile duct biopsies served as controls.

Results

Loss of 5-hmC was seen in 41 of 46 (89.1%) biliary malignancies vs 0 of 20 benign tumors (P < .001), for a sensitivity and specificity of 89.1% and 100%, respectively. Intrahepatic cholangiocarcinoma showed loss of 5-hmC in 11 of 13 (84.6%) cases, similar to the 30 of 33 (90.9%) cases in other biliary adenocarcinomas (P = .61). Similarly, 5-hmC loss was more frequent in distal bile duct adenocarcinomas than in pancreatic ductal adenocarcinomas, at 15 of 17 (88.2%) vs 4 of 12 (33.3%), respectively (P = .0045). There was no difference in the frequency of 5-hmC loss in patients that received neoadjuvant therapy vs those who did not (90.9% vs 88.6%, P  > .99). 5-hmC immunohistochemistry in preoperative biopsies was concordant with the resection specimen in 81.3% (13/16) of cases.

Conclusions

Loss of 5-hmC is not unique to intrahepatic cholangiocarcinoma among biliary carcinomas, but is a useful diagnostic marker differentiating malignancies of the biliary tree from benign mimics.
Good correlation between tacrolimus concentrations using improved CMIA on the Alinity i analyzer and LC-MS/MS method from a reference laboratory but unexpected negative bias with another LC-MS/MS method from a different reference laboratory
Authors: Woodard Kelsey , Kisler Tracey , Dasgupta Amitava
Published: February 2024

Objectives

We compared tacrolimus concentrations obtained by the more recently US Food and Drug Administration–approved tacrolimus assay (CMIA) on the Alinity i analyzer (Abbott Laboratories) with a liquid chromatography/tandem mass spectrometry (LC-MS/MS)–based method from 2 reference laboratories. We also investigated the correlation between the CMIA tacrolimus and Elecsys tacrolimus assays.

Methods

Tacrolimus concentrations were measured in EDTA whole blood by the chemiluminescent microparticle immunoassay (CMIA) using the Alinity i analyzer, and then 2 aliquots were sent to 2 reference laboratories, both using ascomycin as the internal standard for the LC-MS/MS method.

Results

The total precision of the CMIA tacrolimus assay was excellent. When tacrolimus concentrations obtained by the LC-MS/MS method from reference laboratory A were plotted on the x-axis and corresponding CMIA values were plotted on the y-axis, the following regression equation was observed: y = 0.9721x + 1.005 (r = 0.95), indicating no significant bias with the CMIA. However, when tacrolimus values obtained from reference laboratory B were used for comparison, the regression equation was y = 0.7664x + 1.775 (r = 0.93), indicating significant negative bias with the CMIA. When we compared tacrolimus concentrations obtained by reference laboratories A and B, we observed positive bias with tacrolimus concentrations obtained by reference laboratory B. However, tacrolimus concentrations obtained by both CMIA and Elecsys immunoassays were comparable.

Conclusions

Because of good correlation of tacrolimus concentrations using the CMIA and LC-MS/MS from reference laboratory A, our long-term reference laboratory for drug analysis, we concluded that the CMIA on the Alinity i can be used for therapeutic drug monitoring of tacrolimus.
Month-to-month all-cause mortality forecasting: a method allowing for changes in seasonal patterns
Authors: Léger Ainhoa-Elena , Rizzi Silvia
Published: February 2024

Forecasting of seasonal mortality patterns can provide useful information for planning health-care demand and capacity. Timely mortality forecasts are needed during severe winter spikes and/or pandemic waves to guide policy-making and public health decisions. In this article, we propose a flexible method for forecasting all-cause mortality in real time considering short-term changes in seasonal patterns within an epidemiologic year. All-cause mortality data have the advantage of being available with less delay than cause-specific mortality data. In this study, we use all-cause monthly death counts obtained from the national statistical offices of Denmark, France, Spain, and Sweden from epidemic seasons 2012-2013 through 2021-2022 to demonstrate the performance of the proposed approach. The method forecasts deaths 1 month ahead, based on their expected ratio to the next month. Prediction intervals are obtained via bootstrapping. The forecasts accurately predict the winter mortality peaks before the COVID-19 pandemic. Although the method predicts mortality less accurately during the first wave of the COVID-19 pandemic, it captures the aspects of later waves better than other traditional methods. The method is attractive for health researchers and governmental offices for aiding public health responses because it uses minimal input data, makes simple and intuitive assumptions, and provides accurate forecasts both during seasonal influenza epidemics and during novel virus pandemics.
1. ORGANOID DEVELOPMENT IN COLORECTAL CANCER: NEW MODELS FOR PERSONALIZED MEDICINE
Authors: Abad Moret R , Díaz Serrano E , Suárez Enríquez A B , Díaz San Andrés B , Castillo Marcos C , Córdoba L , Fondevila Campo C , Cantero Cid R
Published: February 2024

Introduction

Despite the great advances in recent decades in identifying mechanisms related to tumor progression and resistance to treatment, there are still no safe and effective therapies to treat colorectal cancer (the most common neoplasm in Spain). Organoid models represent a highly promising tool for studying this pathology since they recapitulate, with great precision, the structure and functionality of the original organ.

Methods

At our center, we have generated an extensive collection of human intestinal organoids, including rectum and colon, from biopsies of healthy tissue and tumor tissue from 72 colorectal cancer patients.

For the generation of these models, two different approaches were employed: 1. Organoid generation from intestinal crypts embedded in extracellular matrix droplets; 2. Air-liquid interface (ALI) culture that allows recreating the native microenvironment of the tumor while excluding endogenous infiltrating immune cell populations.

Results

These organoid collections have been highly characterized, confirming that they retain the molecular, structural, and functional characteristics of their tissues of origin. We present the different findings and their correlation.

Conclusion

The technology developed by our research group serves as a tool of great translational value for studying response/resistance mechanisms to current colorectal cancer treatments. Additionally, it serves as a predictive model for drug response, playing a crucial role in defining the efficacy of personalized antineoplastic treatments for each patient and advancing the development of personalized therapies against colorectal cancer.
12. EFFECT OF CETUXIMAB ON LIVER REGENERATION AND COLORECTAL CANCER HEPATIC METASTASIS PROGRESSION IN A MURINE MODEL OF SELECTIVE PORTAL LIGATION
Authors: Tirado-Rodríguez G , Novo I , Rose S , Iturrizaga Correcher S , García Ruiz de Gordejuela A , Ruiz Montesinos I , García-Alonso I , Herrero de la Parte B
Published: February 2024

Introduction

The preferred treatment for patients bearing liver metastases (CRCLM) quite often includes biologic therapies such as cetuximab (anti-EGFR). The aim of this piece of work was to evaluate the effect of cetuximab as a cytoreductive agent for CRCLM in a murine model of selective portal ligation (PVL).

Methods

Male WAG/RijHsd rats were used in this study; thirty MHCCR-bearing animals were subjected to PVL and pretreated with cetuximab (12) or vehicle (12), and another six did not receive any treatment. In addition, another three groups of six animals were included in the study as control: untreated CRCLM-bearing animals, healthy animals subjected to PVL, healthy non-operated animals. Seven days after PVL, the percentage of remaining liver volume (%FRL) and hepatocyte nuclear area were assessed. Serum markers of hepatic, renal and systemic damage were also determined. Tumor volume was assessed by ultrasound, pre- and post-PVL.

Results

Liver regeneration was not substantially altered due to cetuximab treatment, attaining a %FRL between 80-90%; although the area occupied by hepatocyte nuclei was 5% smaller than in the animals of the vehicle group (43.54±9.87 vs. 45.35±9.09μm2; p<0.001). Liver function was also not altered; whereas glucose level was reduced following PVL. Cetuximab reduced tumor growth associated with post-PVL regenerative stimulation (1.12±0.45 vs. 0.53±0.16 ml; p<0.01).

Conclusion

These results suggest that neoadjuvant cetuximab treatment, prior to PVL, is a clinically safe option, not impairing liver regeneration, while blocking tumor progression associated with proliferative hepatic stimulus.
13. KONO-S TYPE ANASTOMOSIS VS LATERO-LATERAL ANASTOMOSIS IN CROHN'S DISEASE: CASE-SERIES REVIEW
Authors: Quinto Llopis S , Sánchez Guillén L , López de Lerma Martínez de Carneros C , Alcaide Quirós M J , López-Rodríguez Arias F , Sánchez Romero A M , Serrano Navidad M , Arroyo Sebastián A
Published: February 2024

Introduction

Up to 80% of patients with Crohn's disease will require surgical treatment in their lifetime. Furthermore, given the high rate of disease recurrence at the site of the anastomosis, many of these patients will require more than one surgery.

In 2003, Kono et al. described the KONO-S anastomosis (KSA) as a surgical option to reduce recurrences. At present, there are still no studies that allow us to affirm, with certainty, this theory.

Methods

A retrospective study was performed reviewing the anastomoses performed in patients with ileocolic Crohn's disease from June 2018 to October 2022.

Results

A total of 15 patients were analyzed. All patients underwent scheduled surgery. The type of anastomosis was KONO-S type in 33.3% (5) and latero-lateral type in 66.7% (10). The approach was laparoscopic in 86.7% (13). In 60% (9) surgery was indicated for stenosing disease.

During the follow-up period, 26.7% (4) presented Clavien Dindo III or IV complications. After hospital discharge, 46.7% (7) of patients presented disease recurrence (either clinical or through imaging), with a recurrence rate of 60% and 20%, respectively, in patients with latero-lateral anastomosis compared to KSA.

Conclusion

KONO-S type anastomosis (KSA) is a type of anastomosis that could reduce recurrences of Crohn's disease. However, more studies with a larger sample size are needed to evaluate this claim.
19. USE OF FERROMAGNETIC SEED SIRIUS PINTUITION® ON THE LOCALIZATION OF NON-PALPABLE TUMORS: PILOT STUDY
Authors: Santana Valenciano A , Rivas Fidalgo S , Corral Moreno S , Gamero Medina V , Pérez Izquierdo C B , Nieto Martos M R , Mena Mateos A , Cabañas Montero L J , Fernández Cebrián J M
Published: February 2024

Introduction

The ferromagnetic seed Sirius Pintuition® is a new technique for the localization of non-palpable tumors. It has several advantages compared to the wire: higher precision of the surgical incision and more comfort for the patient, given the possibility to implant it several days before the surgery.

Methods

To analyze the surgical results after excision of non-palpable breast tumors or axillary lymph nodes guided by ferromagnetic seed between December 2022 and April 2023.

Results

Forty-eight patients were included: 46 breast conservative surgeries and 2 axillary lymph nodes excisions, with women being the majority (46; 95,8%), with a median age of 63,5 (53,75-69). Most of them presented breast tumors (46): invasive ductal carcinoma (25;54,3%), followed by invasive lobulillar carcinoma (5;10,9%). Most frequent localization on the breast was upper external quadrant (19;41,3%), presenting mostly as nodule (35;72,9%) or microcalcifications (8;16,7%). The median size of the tumor was 14,50 mm (10-23). Most seeds were implanted guided by ultrasonography (44; 91,7%). One seed was implanted in 41 patients (85,4%) and 2 seeds in 7 (14,6%), with a median time to surgery of 3 days (1,25-6,75). During surgery a total 5 seeds were accidentally mobilized (10,4%). In 1 patient the resection margins were affected and in 14 the margin was less than 1 mm from the lesion. Eight patients needed re-resection of surgical margins.

Conclusion

The ferromagnetic seed Sirius Pintuition® demonstrated its efficacy in localizing and adequate resection of the lesions. Additionally, it allowed more logistic flexibility thanks to the possibility of implantation several days before surgery.
22. MINIMALLY INVASIVE TREATMENT OF PILONIDAL SINUS: A SINGLE-CENTER COHORT STUDY ON SHORT-TERM OUTCOMES
Authors: Chirivella Fernández A
Published: February 2024

Introduction

Pilonidal sinus is a benign condition that causes infections and abscesses in the intergluteal area, but its physiological explanation is still unclear. There are various surgical techniques to treat it, such as excision with marsupialization, primary closure, and endoscopic pilonidal sinus treatment (EPSiT).

Methods

Forty-six patients between 13 and 23 years of age, who underwent surgery for pilonidal sinus between 01/01/2020 and 31/12/2022, were analyzed. Three techniques were performed: marsupialization, primary closure, and EPSiT by different surgeons in the same hospital complex. A p-value of <0.05 was considered significant.

Results

Significant differences were observed in terms of gender, with a predominance of males, and in the number of interventions performed.

Regarding postoperative results, significant differences were found in bleeding and hematoma formation. Bleeding was greater in the EPSiT group, although hematoma was significantly lower. Furthermore, differences were found in the patient's follow-up time and attendance at healthcare centers for dressing changes. No significant differences were found in other analyzed variables.

Conclusion

The peak incidence of pilonidal sinus is typically estimated during the second decade of life, with a predominant occurrence in males. The maximum recurrence occurs within the first three years after the intervention. This study suggests that EPSiT offers significant advantages by reducing the risk of hematoma and, therefore, wound infection compared to classical techniques. However, we rely on retrospective data from a new technique, with a learning curve and limited follow-up. Additionally, the sample size is limited. Further research with longer follow-up is needed.
Adapting to climate change in char land: investigating community-led initiatives in Bangladesh
Authors: Islam M Rezaul , Ahmad Ifzal , Khan Kanamik K
Published: February 2024

The primary objective of this study was to comprehensively examine the types of climate change, including its magnitudes, and impacts, and to assess the various community-led initiatives implemented in response to these challenges. A quantitative research approach was employed, utilizing structured face-to-face interviews to collect data from 196 household heads in two disaster-affected char land communities, namely Shibchar Upazila in Madaripur District and Zanjira Upazila in Shariatpur District, Bangladesh. The results unveiled the prevalence of frequent hazards such as river erosion, floods, cyclones, and thunderstorms, with river erosion being the most severe. Notably, a significant proportion of respondents (ranging from 80 to 95 percent) indicated that government, non-governmental organizations, and local communities had not adequately undertaken initiatives to address these issues. Furthermore, a noteworthy portion of participants expressed negative sentiments concerning current community affairs and the quality of services provided. The findings of this study hold valuable implications for policy-making, development initiatives, and disaster management strategies within char land communities.
Beta rebound reduces subsequent movement preparation time by modulating of GABAA inhibition
Authors: Zhang Xiangzi , Wang Houmin , Guo Yaqiu , Long Jinyi
Published: February 2024

Post-movement beta synchronization is an increase of beta power relative to baseline, which commonly used to represent the status quo of the motor system. However, its functional role to the subsequent voluntary motor output and potential electrophysiological significance remain largely unknown. Here, we examined the reaction time of a Go/No-Go task of index finger tapping which performed at the phases of power baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds (ballistic/self-paced) in 13 healthy subjects. We found a correlation between the post-movement beta synchronization and reaction time that larger post-movement beta synchronization prolonged the reaction time during Go trials. To probe the electrophysiological significance of post-movement beta synchronization, we assessed intracortical inhibitory measures probably involving GABAB (long-interval intracortical inhibition) and GABAA (short-interval intracortical inhibition) receptors in beta baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds. We found that short-interval intracortical inhibition but not long-interval intracortical inhibition increased in post-movement beta synchronization peak compared with that in the power baseline, and was negatively correlated with the change of post-movement beta synchronization peak value. These novel findings indicate that the post-movement beta synchronization is related to forward model updating, with high beta rebound predicting longer time for the preparation of subsequent movement by inhibitory neural pathways of GABAA.
High cervical anastomosis reduces leakage-related complications after a McKeown esophagectomy
Authors: Chen Chunji , Ding Chengzhi , He Yi , Guo Xufeng
Published: February 2024

OBJECTIVES

Anastomotic leak (AL) is one of the most serious complications after oesophageal cancer surgery. A high cervical anastomosis using a narrow gastric tube based on optimized procedures has the potential to reduce the AL after a McKeown oesophagectomy.

METHODS

A narrow gastric tube was defined as 2–2.5 cm in diameter. Meanwhile, we defined a high anastomosis (HA) and a normal anastomosis (NA) based on the position of the intraoperative cervical anastomosis above or below the level of the inferior thyroid artery, respectively. A total of 533 patients who had a McKeown oesophagectomy from March 2018 to March 2023 were included in this study, including 281 patients in the NA group and 252 patients in the HA group. Potential confounding factors in baseline characteristics were balanced by propensity score matching.

RESULTS

After matching, 190 patients remained in both groups. When comparing the pathological and surgical results, we found that more lymph nodes, both in total number (21.1 ± 10.0 vs 15.8 ± 7.7, P = 0.001) and thoracic part (13.5 ± 7.8 vs10.8 ± 6.1, P = 0.005), were harvested from the HA group . The pathological T and TNM stages of patients in the HA group were earlier than those in the NA group (P = 0.001). Overall postoperative complications (P = 0.001), including pulmonary infection (P = 0.001), AL (P < 0.001), leakage-related pyothorax (P < 0.001), recurrent laryngeal nerve palsy (P = 0.031) and pleural effusion (P < 0.001), were all significantly lower in the HA group. Finally, multivariable logistic regression analysis indicated that HA was an independent protective factor for AL (odds ratio = 0.331, 95% confidence interval: 0.166–0.658; P = 0.002).

CONCLUSIONS

For patients undergoing a McKeown oesophagectomy, a high cervical anastomosis using a narrow gastric tube can effectively reduce leakage-related complications.
Beyond validation: getting wearable activity trackers into cardiovascular care—a discussion paper
Authors: Straiton Nicola , Moons Philip , Verstrael Axel , Liu Mark , Winter Michiel M
Published: February 2024

This paper addresses the challenge of integrating wearable activity trackers (WATs) into cardiovascular disease care. Despite evidence supporting the use of trackers for monitoring and promoting physical activity, implementation challenges persist in clinical settings. The paper emphasizes the lack of systematic, evidence-based implementation approaches for integrating trackers. It underscores the urgent need for stakeholder collaboration between clinicians, patients, implementation scientists, researchers, health and technology partners, and the use of proven implementation science methodologies. This is crucial for bridging the gap and ensuring effective translation of WATs into cardiovascular care, meeting the increasing demand from patients and clinicians.
Healthy eating encouragement and socio-demographic factors associated with cognitive development among pre-schoolers: a cross-sectional evaluation in Nepal
Authors: Sharma Prakash , Budhathoki Chitra Bahadur , Devkota Bhimsen , Singh Jitendra Kumar
Published: February 2024

Background

Cognitive development in pre-schoolers through healthy eating and socio-demographic support is crucial for their later lives. We investigated healthy eating encouragement, socio-demographic factors and their association with cognitive development in pre-schoolers.

Methods

Quantitative data were collected using a multi-stage random sampling between February and April 2021. Pre-schoolers 36 and 71 months and their primary caregivers were recruited from three local government units of Rupandehi district. We compared healthy eating encouragement, socioeconomic and demographic factors with cognitive development using t-test, one-way analysis of variance and multiple linear regression analysis to identify the predictors of the cognitive development among pre-schoolers.

Results

Cognitive development in pre-schoolers is significantly positively associated with age 36–48 months (β = 0.153; 95% CI: 0.12, 13.96), living in a nuclear family (β = 0.121; 95% CI: 0.59, 6.88) and following Buddhism (β = 0.148; 95% CI: 0.88, 14.32). Conversely, children from specific caste/ethnic backgrounds, such as Dalit (β = −0.126; 95% CI: −10.79, −0.68), Janajati (β = −0.237; 95% CI: −6.14, −2.09) and non-Dalit Tarai caste or ethnicity (β = −0.133; 95% CI: −3.46, −0.25) and mothers employed (β = −0.134; 95% CI: −10.62, −1.44) show significantly lower levels of cognitive development.

Conclusions

The finding shows that socioeconomic factors have an influence on cognitive development and also stimulate the adoption of healthy eating encouragement practices.
Brexit and the Legal Legitimacy of the Unitary Patent Court
Authors: Binctin Nicolas , Nard Craig A
Published: February 2024

At no time in recent history has it been more exciting to be a student of European patent law. Over the past ten years Europe has sought to create and restructure a significant portion of its patent law apparatus, including the introduction of a ‘Unitary Patent’ (‘UP’) that has effect in 17 European Union Member States (and counting), and the creation of a Unitary Patent Court (‘UPC’) that entered into force on 1 June 2023. The compelling policies underlying these dramatic changes are well documented, including enhanced uniformity, cost reductions, and other efficiencies. Indeed, the European patent system is poised to welcome international patent actors with a well-thought-out procedural regime.

Yet all good policies must be supported by a legitimate legal foundation. The United Kingdom’s highly publicized and often dramatic departure from the EU has reverberated throughout the European establishment, affecting issues relating to the economy, trade, immigration, labor, and Northern Ireland, to name just some of the most obvious. Perhaps what is not so evident, however, is the adverse legal effect that Brexit has had on the UPC, to such an extent that we are dubious about the court’s legitimacy. Make no mistake, even if we prefer a fully integrated EU solution, we support the creation of UPC and the entire unitary initiative. However, in this paper we argue that it must be done in a manner that is legally principled, which requires an amended and re-ratified Unitary Patent Court Agreement.
The defence of northern Europe: new opportunities, significant challenges
Authors: Friis Karsten , Tamnes Rolf
Published: February 2024

With Finland and Sweden joining NATO, the Nordics will be united for the first time in a military alliance encompassing not only northern Europe but also the broader transatlantic region. It will eventually fortify northern European security, but several obstacles must be overcome first. NATO has done a formidable job since 2014 in updating its defence plans, cumulating in the Deterrence and Defence of the Euro-Atlantic Area (DDA) family of plans approved in Vilnius 2023. Now Finland and Sweden need to be incorporated into these plans. A more challenging task is to implement NATO's New Force Model which is tremendously ambitious. Finland and Sweden's contributions will be important, but new investments must be made. NATO's Command Structure is yet to be fully reformed and fitted to the DDA. Joint Force Command Norfolk must urgently be staffed, without undue politicization in NATO. Nordic defence buildup can draw on regional cooperation in particular in five areas: in strengthening the area's command design through functional double-hatted headquarters; developing close air power cooperation through e.g. a Combined Joint Air Operations Centre; strengthening total defence cooperation across borders and expanding logistical infrastructure; establishing joint intelligence task forces; and joint training and exercises. The contributions of the United States and United Kingdom are indispensable when it comes to upholding the alliance's guarantee in northern Europe. The recent signing of Defense Cooperation Agreements between the US and the Nordics reinforces this—together with an increased presence of air and naval assets in the region. The same applies to the UK and the Joint Expeditionary Force which now has shifted its focus towards northern Europe. This engagement is a crucial addition to Nordic and NATO plans and activities in a period when growth in Nordic defence structures is occurring at a relatively slow pace.
Why so many polyploids? Accounting for environmental stochasticity in unreduced gamete formation lowers the perceived barriers to polyploid establishment
Authors: Gerstner Benjamin P , Wearing Helen J , Whitney Kenneth D
Published: February 2024

While polyploids are common in nature, existing models suggest that polyploid establishment should be difficult and rare. We explore this apparent paradox by focussing on the role of unreduced gametes, as their union is the main route for the formation of neopolyploids. Production of such gametes is affected by genetic and environmental factors, resulting in variation in the formation rate of unreduced gametes (u). Once formed, neopolyploids face minority cytotype exclusion (MCE) due to a lack of viable mating opportunities. More than a dozen theoretical models have explored factors that could permit neopolyploids to overcome MCE and become established. Until now, however, none have explored variability in u and its consequences for the rate of polyploid establishment. Here, we determine the distribution that best fits the available empirical data on u. We perform a global sensitivity analysis exploring the consequences of using empirical distributions of u to investigate effects on polyploid establishment. We determined that in many cases, u is best fit by a log-normal distribution. We found environmental stochasticity in u dramatically impacts model predictions when compared to a static u. Our results help reconcile previous modelling results suggesting high barriers to the polyploid establishment with the observation that polyploids are common in nature.
Violence beyond the Battlefield: Civilian Targeting, Sexual Violence, and Women’s Political Empowerment
Authors: Savun Burcu , Stanton Jessica A , Hartzell Caroline A , Reid Lindsay
Published: February 2024

Research has established links between intrastate conflict and political gains by women following war, suggesting that changes of a positive nature can emerge from the misery of war. While much of the empirical focus on conflicts’ transformative effects has been on battle-related violence, we investigate whether pro-social effects are associated with two other types of violence perpetrated against civilians—one-sided violence and sexual violence. We expect that both one-sided violence and sexual violence spur mobilization, which in turn contributes to gains in women’s political empowerment. Informed by feminist scholarship, we also draw attention to social and political constraints associated with high levels of sexual violence, restrictions that we argue women are unlikely to confront to a similar degree with respect to high levels of one-sided and other forms of violence. We posit that these factors will result in the attenuation of gains in women’s political power in conflicts characterized by high levels of sexual violence. Using cross-national data on civil conflicts for the period 1989–2017, we find that moderate levels of sexual violence are consistently associated with gains in women’s political empowerment, an effect that diminishes in conflicts marked by widespread sexual violence. One-sided violence, on the other hand, is not associated with improvements in women’s political empowerment. Our results demonstrate the importance of considering the different forms of wartime violence, and the differential impacts these forms of violence have on women.​
A case of juvenile-onset ankylosing spondylitis effectively treated with tumour necrosis factor-alpha inhibitor agents
Authors: Sakaguchi Akira , Kondo Naoki , Kakutani Rika , Kinoshita Eiji , Kijima Yasufumi , Kawashima Hiroyuki
Published: February 2024

A 15-year-old girl had experienced hip pain at 11 years of age. At 15 years of age, the patient complained of persistent generalised pain. Her rheumatoid factor and serum matrix metalloproteinase-3 levels were below standard values; there were no inflammatory responses, and the human leukocyte antigen test was negative for B27 and positive for B52 and B62. The bath ankylosing spondylitis disease activity index (BASDAI) value was 8.0 at the time of induction and 3.1 at 6 months after the introduction of adalimumab (at a dose of 40 mg). The BASDAI value improved with an increase in the dose of adalimumab to 80 mg at 8 months after the initial introduction of adalimumab (at 40 mg), although it remained at 4.8 at 16 months after the dose increase. The BASDAI value was 2.6 at 6 months, 2.7 at 1 year, and 1.8 at 1.5 years after the introduction of infliximab, indicating that the patient had progressed well without any adverse events. Based on this case, juvenile ankylosing spondylitis is a differential diagnosis for low back pain and generalised pain since childhood. Tumour necrosis factor (TNF) inhibitors were promptly introduced in this case, although it took 4 years from the initial presentation. TNF inhibitors were effective in treating juvenile ankylosing spondylitis in the present case without any adverse events. This case is notable because juvenile onset ankylosing spondylitis is one of the reasons for severe lumbago since childhood and because TNF inhibitors were administered promptly after diagnosis.
Stellate ganglion block in the treatment of SAPHO syndrome: A case report
Authors: Jiang Chenhao , Cai Liangyu , Zhang Jiannan , Zhou Hongmei
Published: February 2024

Synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare and refractory autoinflammatory disease, and there is no consensus on its treatment. Stellate ganglion block (SGB) blocks sympathetic nerves, ameliorates immune dysfunction, and alleviates stress response, which has been used to treat various chronic pain syndromes, arrhythmias, and post-traumatic stress disorder (PTSD). Also, the SGB has been reported to be successfully used to treat certain skin diseases, autoinflammatory diseases, and menopausal symptoms. In this study, over 3 years of follow-up, we found that SGB successfully intervened the symptoms of SAPHO syndrome, including sternoclavicular joint arthritis and palmoplantar pustulosis.
A novel, semi-automatic procedure for generating slow change blindness stimuli
Authors: Frey Haley G , Koenig Lua , He Biyu J , Brascamp Jan W
Published: February 2024

Change blindness is the phenomenon that occurs when an observer fails to notice what would seem to be obvious changes in the features of a visual stimulus. Researchers can induce this experimentally by including visual disruptions (such as brief blanks) that coincide with the changes in question. However, change blindness can also occur in the absence of these disruptions if a change occurs sufficiently slowly. This “slow” or “gradual” change blindness phenomenon has not been extensively researched. Two plausible practical reasons for this are that there are few slow-change stimuli available, and that it is difficult to collect trial-specific responses without affecting expectations on later trials. Here, we describe a novel, semi-automatic procedure for quickly generating many slow-change stimuli. This procedure creates stimuli that have been specifically designed to allow assessment of change blindness on individual trials without influencing subsequent trials. We include the results of three validation experiments that demonstrate that these stimuli are effective and suitable for use in systematic studies of slow change blindness.
Impacts of workplace verbal aggression classified via text mining on workers’ mental health
Authors: Nishimura Y , Matsumoto S , Sasaki T , Kubo T
Published: February 2024

Background

Exposure to workplace aggression adversely affects workers’ health; however, little is known regarding the impact of specific types of verbal content.

Aims

We aimed to examine the relationship between exposure to several types of aggressive words at work and the victim’s depressive symptoms and sleep disturbance using text mining.

Methods

We conducted a longitudinal survey with 800 workers in wholesale and retail companies; of which, 500 responded to the follow-up survey. The Centre for Epidemiologic Studies—Depression Scale and Pittsburgh Sleep Quality Index were filled out by the participants, and their responses were analysed by logistic regression to evaluate the risk of depression or sleep problems. We collected exact aggressive words encountered at work over the past year as a dependent variable and classified it into four types using text mining, such as words criticizing one’s performance.

Results

The follow-up rate was 63%. Exposure to words threatening one’s life showed a significant relationship with the risk of depression (odds ratio [OR] = 13.94, 95% confidence interval [CI] = 1.76–110.56). The exposure to words criticizing one’s job performance is significantly related to the risk of sleep disturbance (OR = 5.56, 95% CI = 2.08–14.88).

Conclusions

These findings suggest that different contents of verbal aggression can have different impacts on workers’ health. This indicates that not only overtly threatening and abusive language but also words related to one’s performance can be a risk factor for workers, depending on how they are delivered. To mitigate the adverse effects, promoting effective communication and cultivating psychological detachment from work may be beneficial.
Disruption of the bacterial OLE RNP complex impairs growth on alternative carbon sources
Authors: Lyon Seth E , Wencker Freya D R , Fernando Chrishan M , Harris Kimberly A , Breaker Ronald R
Published: February 2024

Ornate, large, extremophilic (OLE) RNAs comprise a class of large noncoding RNAs in bacteria whose members form a membrane-associated ribonucleoprotein (RNP) complex. This complex facilitates cellular adaptation to diverse stresses such as exposure to cold, short-chain alcohols, and elevated Mg2+ concentrations. Here, we report additional phenotypes exhibited by Halalkalibacterium halodurans (formerly called Bacillus halodurans) strains lacking functional OLE RNP complexes. Genetic disruption of the complex causes restricted growth compared to wild-type cells when cultured in minimal media (MM) wherein glucose is replaced with alternative carbon/energy sources. Genetic suppressor selections conducted in glutamate MM yielded isolates that carry mutations in or near genes relevant to Mn2+ homeostasis (ykoY and mntB), phosphate homeostasis (phoR), and putative multidrug resistance (bmrCD). These functional links between OLE RNA, carbon/energy management, and other fundamental processes including protein secretion are consistent with the hypothesis that the OLE RNP complex is a major contributor to cellular adaptation to unfavorable growth conditions.
Good models borrow, great models steal: intellectual property rights and generative AI
Authors: Chesterman Simon
Published: February 2024

Two critical policy questions will determine the impact of generative artificial intelligence (AI) on the knowledge economy and the creative sector. The first concerns how we think about the training of such models—in particular, whether the creators or owners of the data that are “scraped” (lawfully or unlawfully, with or without permission) should be compensated for that use. The second question revolves around the ownership of the output generated by AI, which is continually improving in quality and scale. These topics fall in the realm of intellectual property, a legal framework designed to incentivize and reward only human creativity and innovation. For some years, however, Britain has maintained a distinct category for “computer-generated” outputs; on the input issue, the EU and Singapore have recently introduced exceptions allowing for text and data mining or computational data analysis of existing works. This article explores the broader implications of these policy choices, weighing the advantages of reducing the cost of content creation and the value of expertise against the potential risk to various careers and sectors of the economy, which might be rendered unsustainable. Lessons may be found in the music industry, which also went through a period of unrestrained piracy in the early digital era, epitomized by the rise and fall of the file-sharing service Napster. Similar litigation and legislation may help navigate the present uncertainty, along with an emerging market for “legitimate” models that respect the copyright of humans and are clear about the provenance of their own creations.
Randomized controlled internal pilot trial of a diversion programme for adolescents in police custody who possess illicit substances
Authors: Coulton Simon , Hendrie Nadine , Vass Rosa , Gannon Theresa , Wooton Agnes , Rushworh-Claeys Jennifer , Sinetos Jake
Published: February 2024

Background

Adolescents involved in criminal proceedings are significantly more likely to re-offend than a similar population diverted away from criminal justice. Adolescents who use substances and offend are at higher risk of experiencing negative social, psychological and physical problems that often persist into adulthood. There is some evidence that brief interventions combined with appropriate psychoeducation may be effective in reducing adolescent substance use.

Methods

Prospective two-armed, individually randomized internal pilot randomized controlled trial (RCT) with follow-up at 6 months. Young people across three police forces—Kent, Cornwall and Sefton—arrested in possession of class B or C illicit substances were randomly allocated to receive the ReFrame intervention or business as usual. In total, 102 participants were eligible of whom 76 consented and 73 were followed up at 6 months. Outcomes addressed offending behaviour, frequency of substance use, wellbeing and mental health. The study was conducted between February and December 2022.

Results

All progression criteria were met, 80% of those eligible consented, 96% adhered to their allocated treatment and 88% were followed up at the primary endpoint.

Conclusions

The feasibility of conducting the pilot trial was a success and it will now proceed to a definitive RCT.
Medication-induced central sleep apnea: a unifying concept
Authors: Javaheri Shahrokh , Randerath Winfried J , Safwan Badr M , Javaheri Sogol
Published: February 2024

Medication-induced central sleep apnea (CSA) is one of the eight categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioid medications including sodium oxybate, baclofen, valproic acid, gabapentin, and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid, and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.
Combined estrogen-progestin oral contraceptives and female sexuality: an updated review
Authors: Krapf Jill M , Goldstein Andrew T
Published: February 2024

Introduction

Sexual side effects of combined oral contraceptives (COCs) have not been fully understood, but increasing evidence prompts broader risk/benefit evaluation and merits inclusion in counseling on contraceptive options.

Objectives

The study sought to explore the impact of combined estrogens–progestin oral contraceptives on components of female sexuality, including sexual desire, anatomic genitourinary changes, lubrication, orgasm, provoked vestibulodynia, well-being, body image, partner preference, and relationship stability.

Methods

A literature review was performed between April 2023 and January 2024 exploring the association between combined oral contraceptive pills and sexual health.

Results

Although COCs decrease free testosterone, it is unclear if COCs affect sexual function, including desire. Antiandrogenic COCs do seem to have a negative effect on sexual arousal, lubrication, and orgasm. Provoked vestibulodynia may be related to early onset of COC use, low-estrogen pills, and antiandrogenic progestins. Emotional and sexual side effects are strong predictors of COC discontinuation. Longitudinal data indicate that using COCs when meeting and selecting a partner has implications on sexual satisfaction and relationship length. Analysis of data is complicated by various doses and forms of estrogen and progestin in COCs, which have changed over time.

Conclusion

Lack of randomized placebo-controlled studies and heterogenicity in study design hampers generalized statements about the effects of COCs on sexual function. Despite these challenges, consideration of sexual dysfunction when presenting and prescribing hormonal contraception is essential for informed consent, shared decision making, and ensuring reliable contraceptive choices.
Exercise‐induced β‐hydroxybutyrate promotes Treg cell differentiation to ameliorate colitis in mice
Authors: Hao Fengqi , Tian Miaomiao , Wang Huiyue , Li Shuo , Wang Xinyu , Jin Xin , Wang Yang , Jiao Yang , Tian Meihong
Published: February 2024

Increasing attention is being paid to the mechanistic investigation of exercise‐associated chronic inflammatory disease improvement. Ulcerative colitis (UC) is one type of chronic inflammatory bowel disease with increasing incidence and prevalence worldwide. It is known that regular moderate aerobic exercise (RMAE) reduces the incidence or risk of UC, and attenuates disease progression in UC patients. However, the mechanisms of this RMAE's benefit are still under investigation. Here, we revealed that β‐hydroxybutyrate (β‐HB), a metabolite upon prolonged aerobic exercise, could contribute to RMAE preconditioning in retarding dextran sulfate sodium (DSS)‐induced mouse colitis. When blocking β‐HB production, RMAE preconditioning‐induced colitis amelioration was compromised, whereas supplementation of β‐HB significantly rescued impaired β‐HB production‐associated defects. Meanwhile, we found that RMAE preconditioning significantly caused decreased colonic Th17/Treg ratio, which is considered to be important for colitis mitigation; and the downregulated Th17/Treg ratio was associated with β‐HB. We further demonstrated that β‐HB can directly promote the differentiation of Treg cell rather than inhibit Th17 cell generation. Furthermore, β‐HB increased forkhead box protein P3 (Foxp3) expression, the core transcriptional factor for Treg cell, by enhancing histone H3 acetylation in the promoter and conserved noncoding sequences of the Foxp3 locus. In addition, fatty acid oxidation, the key metabolic pathway required for Treg cell differentiation, was enhanced by β‐HB treatment. Lastly, administration of β‐HB without exercise significantly boosted colonic Treg cell and alleviated colitis in mice. Together, we unveiled a previously unappreciated role for exercise metabolite β‐HB in the promotion of Treg cell generation and RMAE preconditioning‐associated colitis attenuation.
Treatment of Gamma Hydroxybutyrate Withdrawal in a Pregnant Female: A Case Report
Authors: Joyce Shannon , Lea Sarah , Woolner Megan , Leddy Amanda
Published: February 2024

Background

Gamma hydroxybutyrate (GHB) is used illicitly for its sedative hypnotic effects, and those who take it regularly are at risk of developing a substance use disorder. Withdrawal from GHB can include severe symptoms that may require medical management. For GHB use and withdrawal during pregnancy, there are no evidence- or practice-based guidelines to follow, and there is only minimal research literature.

Case Summary

We present the case of a 32-year-old woman, G1P0 at 29 weeks and 6 days of gestation, admitted to the perinatal unit at a tertiary hospital for GHB withdrawal management and stabilization. GHB withdrawal was managed with a combination of baclofen and diazepam. We report the dosing and tapering of these medications throughout her 14-day admission. Withdrawal symptoms were well managed with this medication protocol, and she did not experience any features of complicated withdrawal. The patient later presented to hospital in preterm labor and precipitously delivered a healthy, preterm infant male at 34 weeks and 5 days of gestation. At 7 months postpartum, the patient continued to engage with perinatal addiction service, reported no use of GHB since her admission, and was parenting her healthy son.

Clinical Significance

There is a paucity of guidelines for managing GHB withdrawal in pregnancy. This case demonstrates good clinical outcomes administering a short-term combination of diazepam and baclofen during the third trimester of pregnancy. This case helps to fill a gap in the literature and may inform future research or clinical decision-making in similar situations.