bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and epidemiologic evaluation of a 2020 chikungunya outbreak in Cambodia
Authors: Rachmat Agus , Kelly Gerard C. , Hontz Robert D. , Supaprom Chonthida , Heang Vireak , Hip Phireak , Garcia-Rivera Jose A. , Prom Satharath , Chhea Chhorvann , Sutherland Ian W. , Corson Karen S. , Letizia Andrew G.
Published: December 2022

Background

In 2020, the Kingdom of Cambodia experienced a nationwide outbreak of chikungunya virus (CHIKV). Despite an increase in the frequency of outbreaks and expanding geographic range of CHIKV, diagnostic challenges remain, and limited surveillance data of sufficient granularity are available to characterize epidemiological profiles and disease dynamics of the virus.

Methods

An ongoing and long-standing cross-sectional study of acute undifferentiated febrile illness (AUFI) in Cambodia was leveraged to describe the disease epidemiology and characterize the clinical presentation of patients diagnosed with CHIKV during the 2020 outbreak. Participants presenting with AUFI symptoms at ten study locations provided acute and convalescent blood samples and were tested for CHIKV using a reverse transcription-polymerase chain reaction (RT-PCR) and serological diagnostic methods including IgM and IgG. Acute and follow-up clinical data were also collected.

Results

From 1194 participant blood samples tested, 331 (27.7%) positive CHIKV cases were detected. Most CHIKV positive individuals (280, 84.6%) reported having a fever 3 to 4 days prior to visiting a health facility. Symptoms including chills, joint pain, nausea, vomiting, and lesions were all statistically significant among CHIKV positive participants compared to CHIKV negative AUFI participants. Cough was negatively associated with CHIKV positive participants. Positivity proportions were significantly higher among adults compared to children. No significant difference was found in positivity proportion between rainy and dry seasons during the outbreak. Positive CHIKV cases were detected in all study site provinces, with the highest test positivity proportion recorded in the rural northeast province of Kratie.

Conclusions

Surveillance data captured in this study provided a clinical and epidemiological characterization of positive CHIKV patients presenting at selected health facilities in Cambodia in 2020, and highlighted the widespread distribution of the outbreak, impacting both urban and rural locations. Findings also illustrated the importance of utilizing both RT-PCR and serological testing for effective CHIKV surveillance.
RESOLVE-DWI-based deep learning nomogram for prediction of normal-sized lymph node metastasis in cervical cancer: a preliminary study
Authors: Qian Weiliang , Li Zhisen , Chen Weidao , Yin Hongkun , Zhang Jibin , Xu Jianming , Hu Chunhong
Published: December 2022

Background

It is difficult to predict normal-sized lymph node metastasis (LNM) in cervical cancer clinically. We aimed to investigate the feasibility of using deep learning (DL) nomogram based on readout segmentation of long variable echo-trains diffusion weighted imaging (RESOLVE-DWI) and related patient information to preoperatively predict normal-sized LNM in patients with cervical cancer.

Methods

A dataset of MR images [RESOLVE-DWI and apparent diffusion coefficient (ADC)] and patient information (age, tumor size, International Federation of Gynecology and Obstetrics stage, ADC value and squamous cell carcinoma antigen level) of 169 patients with cervical cancer between November 2013 and January 2022 were retrospectively collected. The LNM status was determined by final histopathology. The collected studies were randomly divided into a development cohort (n = 126) and a test cohort (n = 43). A single-channel convolutional neural network (CNN) and a multi-channel CNN based on ResNeSt architectures were proposed for predicting normal-sized LNM from single or multi modalities of MR images, respectively. A DL nomogram was constructed by incorporating the clinical information and the multi-channel CNN. These models’ performance was analyzed by the receiver operating characteristic analysis in the test cohort.

Results

Compared to the single-channel CNN model using RESOLVE-DWI and ADC respectively, the multi-channel CNN model that integrating both two MR modalities showed improved performance in development cohort [AUC 0.848; 95% confidence interval (CI) 0.774–0.906] and test cohort (AUC 0.767; 95% CI 0.613–0.882). The DL nomogram showed the best performance in development cohort (AUC 0.890; 95% CI 0.821–0.938) and test cohort (AUC 0.844; 95% CI 0.701–0.936).

Conclusion

The DL nomogram incorporating RESOLVE-DWI and clinical information has the potential to preoperatively predict normal-sized LNM of cervical cancer.
Parental information about the option to apply for pregnancy termination after the detection of a congenital abnormality and factors influencing parental decision-making: a cohort study
Authors: Hjort-Pedersen Karina , Olesen Annette Wind , Garne Ester , Toerring Pernille Mathiesen , Wu Chunsen , Sperling Lene
Published: December 2022

Background

The detection of an abnormality during prenatal screening implies that the parents are informed about possible treatment and management of the pregnancy, birth, and postnatal course. This information should enable the parents to make decisions regarding the pregnancy, especially in cases where termination of pregnancy may be an option. The objectives of this study were to investigate how often doctors informed parents about pregnancy termination when the fetus had an anomaly and which demographic factors were related to parental decision-making.

Methods

This was a retrospective cohort study with prospectively collected data of fetuses diagnosed with an abnormality during prenatal screening between 2014 and 2016 in Denmark. We categorized the abnormalities into five long-term prognosis groups and analyzed their association with the doctor provided information about termination. We tested the association between demographic variables and parental decisions using univariate and multivariate statistical analyses.

Results

Three hundred and twenty fetuses were diagnosed with an abnormality. In 67% of these cases, the parents were informed about termination. All parents whose fetus had a lethal prognosis were informed about termination. By comparison, the parents of 98% of fetuses with genetic disorders, 96% of fetuses with poor prognosis, 69% of fetuses with uncertain prognosis, and 12% of fetuses with good prognosis were informed about termination. Of these parents, 92% chose to terminate. A lethal long-term prognosis was the only factor related to parental decision to terminate a pregnancy.

Conclusions

Doctors mainly informed parents about the option of pregnancy termination for conditions with a poor or lethal long-term prognosis or for genetic disorders. Only conditions with a lethal prognosis were significantly related to the parental decision to terminate the pregnancy.
Effect of EGFR amplification on the prognosis of EGFR-mutated advanced non–small-cell lung cancer patients: a prospective observational study
Authors: Peng Duanyang , Liang Pingan , Zhong Congying , Xu Peng , He Yanqing , Luo Yuxi , Wang Xia , Liu Anwen , Zeng Zhimin
Published: December 2022

Background

Epidermal growth factor receptor (EGFR) amplification refers to the copy number increase of EGFR gene, and is often identified as a “bypass” way of Epidermal growth factor receptor Tyrosine kinase inhibitors (EGFR-TKI) resistance. We aimed to explore the effect of EGFR amplification on EGFR mutation treatment-naive advanced non-squamous non-small cell lung cancer (NSCLC) patients.

Methods

We conducted a prospective observational study in single center, enrolling advanced non-squamous NSCLC patients receiving Tyrosine kinase inhibitors (TKIs) between March 3, 2019, and February 1, 2022. Next-generation sequencing (NGS) was used to detect genetic alterations in tumor tissue samples. Progression-free survival (PFS) curves were performed using the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate factors affecting the efficacy of TKIs.

Results

A total of 117 treatment-naive advanced NSCLC patients were identified in this study. EGFR amplification was found in 22 of 117 (18.8%) patients with EGFR mutations. Of 22 patients with EGFR amplification, 10 patients harbored EGFR 19 del, 11 patients with 21-L858R. The median follow-up time was 22.47 months. The median PFS of the patients with or without EGFR amplification was 8.25 months and 10.67 months, respectively (log-rank test, P = 0.63). In multivariate analysis, EGFR amplification was not an independent prognosis factor for the patients receiving first-line TKIs [HR = 1.38, 95%CI (0.73–2.58), P = 0.321]. Subgroup analysis revealed that EGFR amplification is a risk factor for progression in the brain metastasis population. [HR = 2.28, 95%CI (1.01, 5.14), P = 0.047].

Conclusion

EGFR amplification is not an independent prognosis factor for PFS in advanced non-squamous NSCLC patients receiving first-line TKIs. However, it is an independent risk factor for PFS in the brain metastasis population.
Feasibility of edoxaban for asymptomatic cancer-associated thrombosis in Japanese patients with gastrointestinal cancer: ExCAVE study
Authors: Nakamura Michio , Ishiguro Atsushi , Dazai Masayoshi , Kawamoto Yasuyuki , Yuki Satoshi , Sogabe Susumu , Hosokawa Ayumu , Sawada Kentaro , Muto Osamu , Izawa Naoki , Nakashima Koji , Horie Yoshiki , Yagisawa Masataka , Kajiura Shinya , Ando Takayuki , Mitsuhashi Yosuke , Sunakawa Yu , Kikuchi Yasuka , Komatsu Yoshito
Published: December 2022

Background

Although initial therapy with a parenteral anticoagulant is required before edoxaban, this strategy is frequently avoided in actual clinical practice because of its complexity. This study assessed the feasibility of edoxaban without initial heparin usage for asymptomatic cancer-associated thrombosis (CAT) in Japanese patients with gastrointestinal cancer (GIC) at high risk of bleeding.

Methods

In this multicenter prospective feasibility study conducted at 10 Japanese institutions, patients with active GIC who developed accidental asymptomatic CAT during chemotherapy were recruited. Edoxaban was orally administered once daily without initial parenteral anticoagulant therapy within 3 days after detecting asymptomatic CAT. The primary outcome was the incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) during the first 3 months of edoxaban administration.

Results

Of the 54 patients enrolled from October 2017 to September 2020, one was excluded because of a misdiagnosis of CAT. In the remaining 53 patients, the primary outcome occurred in six patients (11.3%). MB occurred in four patients (7.5%), including gastrointestinal bleeding in three patients and intracranial hemorrhage in one patient. CRNMB occurred in two patients (3.8%), including bleeding from the stoma site and genital bleeding in one patient each. There were no deaths attributable to bleeding, and all patients who experienced MB or CRNMB recovered.

Conclusions

The risk of bleeding after edoxaban without heparin pretreatment was acceptable, demonstrating new treatment options for asymptomatic CAT in patients with GIC.
A phase II study of daily encorafenib in combination with biweekly cetuximab in patients with BRAF V600E mutated metastatic colorectal cancer: the NEW BEACON study
Authors: Eriksen Martina , Pfeiffer Per , Rohrberg Kristoffer Staal , Yde Christina Westmose , Petersen Lone Nørgård , Poulsen Laurids Østergaard , Qvortrup Camilla
Published: December 2022

Background

Patients with BRAF V600E mutated metastatic colorectal cancer (mCRC) have a poor prognosis. The introduction of BRAF targeted therapy with encorafenib and weekly administered cetuximab have shown improved survival with a median progression free survival (PFS) of 4.3 months. However, a regimen with cetuximab given every second week may have comparable efficacy and is more convenient for patients. While BRAF targeted therapy is a new standard therapy in pre-treated patients with BRAF V600E mutated mCRC, resistance invariably occurs and is an emerging challenge. The aim of this study is to investigate the efficacy and tolerability of cetuximab given every second week in combination with daily encorafenib and to explore the correlation between markers of resistance and outcome.

Methods

The study is an open label, single arm, phase II study, investigating the efficacy and tolerability of cetuximab given every second week in combination with encorafenib in patients with BRAF V600E mutated mCRC. Furthermore, we will be investigating mechanisms of response and resistance against BRAF targeted therapy though comprehensive genomic profiling on tumor tissue and blood for circulating tumor DNA analysis. A total of 53 patients (19 + 34 in two steps) will be included according to Simon’s optimal two stage design. The primary end point of the study is 2 months PFS rate.

Discussion

By combining BRAF inhibitor with cetuximab given every second week we can halve the number of visits in the hospital compared to the currently approved regimen with weekly cetuximab. This seems particularly relevant in a group of patients with a median overall survival of 9.3 months. Resistance after initial response to targeted therapy can be either adaptive (e.g., epigenetic, or transcriptomic alterations) or acquired (selective genetic alterations - e.g., activating de novo mutations) resistance. It is of great importance to untangle these complex mechanisms of resistance in patients with BRAF V600E mutated mCRC to improve treatment strategies in the future potentially even further.

Trial registration

EU Clinical Trial Register, Eudract no. 2020-003283-10. Registered on 11 November 2020.
Clinical and economic burden of physician-diagnosed influenza in adults during the 2017/2018 epidemic season in Spain
Authors: Gil-de-Miguel Ángel , Martinón-Torres Federico , Díez-Domingo Javier , de Lejarazu Leonardo Raúl Ortiz , Pumarola Tomàs , Carmo Mafalda , Drago Georgina , López-Belmonte Juan Luis , Bricout Hélène , de Courville Caroline , Margüello Esther Redondo
Published: December 2022

Background

Influenza is an acutely debilitating respiratory infection, contributing significantly to outpatient visits and hospitalizations. Spain lacks comprehensive and updated data on the burden of influenza, particularly in the outpatient setting. Our study aimed to fill this gap by estimating the clinical and economic burden of physician-diagnosed influenza cases in adults from four Spanish regions, stratified by age groups and presence of comorbidities.

Methods

A retrospective cost-of-illness study was conducted using data from an electronic medical records database from the National Healthcare Service (NHS) of four Spanish regions for individuals aged ≥ 18 years diagnosed for influenza during the 2017/2018 epidemic season. Health resource utilization and related cost data were collected, including primary care visits, referrals to other specialists, visits to the emergency department, hospitalizations, and prescribed medicines.

Results

The study reported a total of 28,381 patients aged ≥ 18 years diagnosed with influenza, corresponding to 1,804 cases per 100,000 population. Most patients were aged < 65 years: 60.5% (n = 17,166) aged 18–49 and 26.3% (n = 7,451) 50–64 years. A total of 39.2% (n = 11,132) of patients presented a comorbidity. Cardiovascular diseases were the most common comorbidity reported along with influenza. The mean healthcare cost per case was estimated at €235.1 in population aged 18–49 years, increasing by 1.7 and 4.9 times in those aged 50–64 (€402.0) and ≥ 65 (€1,149.0), respectively. The mean healthcare cost per case was 3.2 times higher in patients with comorbidities. The total healthcare cost of medically attended influenza cases was mainly driven by primary care (45.1%) and hospitalization (42.0%). Patients aged 18–64 years old accounted for 61.9% of the costs of medically attended influenza. Irrespective of age, patients with comorbidities accounted for 67.1% of costs.

Conclusions

Season 2017/2018 was associated with a considerable burden of influenza in Spain, which increased with age and presence of comorbidities. Individuals with comorbidities accounted for most of the costs of influenza. Results suggest that population aged 18–64 years old is generating the highest share of costs to the NHS when all healthcare costs are considered. Preventive strategies targeting subjects with comorbidities, regardless of age, should be warranted.
Perceived controllability of a SARS-CoV-2 infection: an investigation of intersectional differences
Authors: Neugebauer Till , Wahidie Diana , Erdsiek Fabian , Yilmaz-Aslan Yüce , Brzoska Patrick
Published: December 2022

Background

The perceived ability to influence an infection with SARS-CoV-2 has an impact on compliance with protective measures. Factors influencing perceived controllability are not yet fully known. The aim of this study was to identify intersectional differences in perceived controllability. Insights into these intersectional differences could help to develop user-centered strategies to improve the acceptance of protective measures.

Methods

Data from the seventh wave of the German Ageing Survey (DEAS) was used to investigate differences in the population regarding the perceived controllability. The role of socio-demographic and socio-economic predictors was investigated using multivariable linear regression modeling. Intersectional differences were examined using interaction terms.

Results

Information on 4,823 respondents aged 46 to 100 years were available, of which 50.9% were female. Migration status (yes vs. no: β = -0.27; 95%-CI = -0.48,-0.06), education level (high vs. low: β = 0.31; 95%-CI: 0.08, 0.55) and employment status (retired vs. employed: β = 0.33; 95%-CI: 0.19, 0.48) were found to be significantly influencing perceived controllability. Interaction effects were found with respect to sex and migration status, with migrant women rating their perceived controllability lower than non-migrant women (β = -0.51; 95%-CI = -0.80, -0.21), while no differences were evident between migrant and non-migrant men (β = -0.02; 95%-CI = -0.32, 0.28). Further intersectional differences were not observed.

Conclusions

The results show that intersectional differences in perceived controllability occur especially between migrant and non-migrant women. Possible causes may lie in language barriers, which in connection with lower health literacy may affect perceived controllability. Dedicated efforts to improve controllability among older adults, those with lower educational attainment and migrant women are warranted.
Alveolus analysis: a web browser-based tool to analyze lung intravital microscopy
Authors: Politowicz Alexander L. , Burks Andrew T. , Dong Yushen , Htwe Yu Maw , Dudek Steven M. , Elisabeta Marai G. , Belvitch Patrick
Published: December 2022

Background

Acute lung injury and the acute respiratory distress syndrome are characterized by pulmonary inflammation, reduced endothelial barrier integrity and filling of the alveolar space with protein rich edema fluid and infiltrating leukocytes. Animal models are critical to uncovering the pathologic mechanisms of this devastating syndrome. Intravital imaging of the intact lung via two-photon intravital microscopy has proven a valuable method to investigate lung injury in small rodent models through characterization of inflammatory cells and vascular changes in real time. However, respiratory motion complicates the analysis of these time series images and requires selective data extraction to stabilize the image. Consequently, analysis of individual alveoli may not provide a complete picture of the integrated mechanical, vascular and inflammatory processes occurring simultaneously in the intact lung. To address these challenges, we developed a web browser-based visualization application named Alveolus Analysis to process, analyze and graphically display intravital lung microscopy data.

Results

The designed tool takes raw temporal image data as input, performs image preprocessing and feature extraction offline, and visualizes the extracted information in a web browser-based interface. The interface allows users to explore multiple experiments in three panels corresponding to different levels of detail: summary statistics of alveolar/neutrophil behavior, characterization of alveolar dynamics including lung edema and inflammatory cells at specific time points, and cross-experiment analysis. We performed a case study on the utility of the visualization with two members or our research team and they found the tool useful because of its ability to preprocess data consistently and visualize information in a digestible and informative format.

Conclusions

Application of our software tool, Alveolus Analysis, to intravital lung microscopy data has the potential to enhance the information gained from these experiments and provide new insights into the pathologic mechanisms of inflammatory lung injury.
Predictors and tactics for revision surgery in lateral lumbar interbody fusion
Authors: Wang Weijian , Li Jiaqi , Xu Yafei , Luo Yun , Ding Wenyuan , Zhang Wei
Published: December 2022

Background

The purpose of this study is to analyze the factors affecting the revision of lateral lumbar interbody fusion (LLIF), and to summarize the complications and decision-making strategies for revision surgery after LLIF.

Methods

We retrospectively reviewed 21 cases suffered from a revision surgery after LLIF in our department from May 2017 to June 2020, with a mean follow-up of 14 months (12-25months). We collected X-ray plain films, CT (computed tomography), MRI (magnetic resonance imaging) and medical records of all patients undergoing LLIF surgery, then analyzed the reasons for revision and summarized the revision strategies in different situations. We analysed correlations between revision surgery and several factors, including age, body mass index (BMI), sex, bone quality, mode of internal fixation, spinal stenosis, postperative foraminal stenosis, disc height. Then we brought the different indicators into logistic regression to find out the risk factors of revision after LLIF. All these patients were evaluated by Quality-of-life outcomes. Univariate statistical analysis was performed using T-tests, Mann-Whitney U tests and Chi square tests.

Results

Of the 209 cases of LLIF, 21 patients underwent postoperative revision. All revision surgeries were successfully completed. The reasons for revision included vascular injury, unsatistactory implant placement, internal spinal instrumentation failure, cage migration, indirect decompression failure and infection. Indirect decompression failure was the most common indications for revision. Clinical status was apparently improved in ODI scores and VAS scores. Revision surgery did not impact long-term effect and satisfaction. Postoperative foraminal stenosis is a positive predictor for a revision surgical procedure.

Conclusion

Patients with postoperative foraminal stenosis are at higher risk of undergoing revision surgery after lateral lumbar interbody fusion. The correct choice of revision surgery can achieve satisfactory clinical results.
Combined arthroscopic release with corticosteroid hydrodilatation versus corticosteroid hydrodilatation only in treating freezing-phase primary frozen shoulder: a randomized clinical trial
Authors: Dai Zhu , Liu Quanhui , Liu Bo , Long Ke , Liao Ying , Wu Biao , Huang Wen , Liu Chao
Published: December 2022

Background

There has been no ideal treatment for freezing-phase frozen shoulder to rapidly relieve pain and improve joint mobility. No any other team directly compared the effectiveness of combination of arthroscopic release and corticosteroid hydrodilatation with corticosteroid hydrodilatation only in treatment of freezing-phase frozen shoulder.

Methods

Seventy-two patients with freezing-phase frozen shoulder were randomly assigned to combined arthroscopic release with corticosteroid hydrodilatation (group A) or corticosteroid hydrodilatation only (group B). Clinical states were examined at baseline and periodically (Weeks 1, 4, 12, 24 and 1 year) after intervention by passive ROM; visual analog scale (VAS); UCLA and Disabilities of the Arm, Shoulder, and Hand (DASH) score.

Results

The passive ROM, VAS, UCLA and DASH scores always improved along the time points (all p < 0.01). The passive abduction (pAB), passive forward flexion (pFL), passive external rotation (pER), passive internal rotation (pIR) were better in group A than in group B at Week 1, 4, 12, 24 (all p < 0.01). At 1 year post-operation, the pFL and pIR were better in group A than in group B (all p < 0.01). VAS scores of group A were similar with those of group B (all p > 0.01), the differences between group A and group B were all lower than minimal clinically important difference (MCID). At Week 12, the UCLA sores and DASH scores were 26.8 ± 3.8, 14.2 ± 2.0 in group A versus 22.3 ± 3.4, 22.5 ± 3.1 in group B (all p < 0.01). At Week 24 post-operation, there were 32.7 ± 2.0, 9.8 ± 1.5 in group A versus 26.3 ± 3.6, 17.5 ± 3.5 in group B (all p < 0.01). At 1 year post-operation, there were 34.5 ± 0.8, 1.7 ± 1.5 in group A versus 32.1 ± 2.3, 8.8 ± 2.8 in group B (all p < 0.01), the differences of UCLA scores between group A and group B at Week 24 was higher than the MCID. There were no complications such as infection, nerve or vascular injury.

Conclusions

Combined arthroscopic release with corticosteroid hydrodilatation would yield better results in passive ROM and function than corticosteroid hydrodilatation only.

Trial registration

ChiCTR1900024235, July 2, 2019 (Retrospectively registered).
Familial hypocalciuric hypercalcaemia type 1 caused by a novel heterozygous missense variant in the CaSR gene, p(His41Arg): two case reports
Authors: Courtney Aoife , Hill Arnold , Smith Diarmuid , Agha Amar
Published: December 2022

Background

Familial hypocalciuric hypercalcaemia (FHH) is a rare, inherited disorder of extracellular calcium sensing. It is clinically characterised by mild to moderate parathyroid hormone dependent hypercalcaemia, an autosomal dominant pattern of inheritance, and a normal to reduced urinary calcium excretion in spite of high serum calcium.

Case presentation

We report two cases of FHH in a family caused by a novel pathogenic missense variant in the CaSR gene, p. His41Arg. Case 1, describes a 17 year old female with no significant past medical history, admitted with acute appendicitis requiring laparoscopic appendectomy and reporting a six month history of polydipsia. Routine investigations were significant for hypercalcaemia, corrected calcium 3.19 mmol/L (2.21-2.52mmol/L), elevated parathyroid hormone of 84pg/ml (15-65pg/ml) and a low 24-hour urine calcium of 0.75mmol/24 (2.50-7.50mmol/24). She was initially managed with intravenous fluids and Zolendronic acid with temporary normalisation of calcium though ultimately required commencement of Cinacalcet 30 mg daily for persistent symptomatic hypercalcaemia. Genetic analysis was subsequently positive for the above variant. Case 2, a 50-year-old female, was referred to the endocrine outpatient clinic for the management of type 2 diabetes and reported a longstanding history of asymptomatic hypercalcaemia which had not been investigated previously. Investigation revealed hypercalcaemia; corrected calcium of 2.6 mmol/L (reference range: 2.21–2.52 mmol/L); PTH of 53.7ng/L (reference range: 15–65 ng/L) and an elevated 24-hour urine calcium of 10 mmol/24 (2.50–7.50 mmol/24hr) with positive genetic analysis and is managed conservatively. Despite sharing this novel mutation, these cases have different phenotypes and their natural history is yet to be determined. Two further relatives are currently undergoing investigation for hypercalcaemia and the family have been referred for genetic counselling.

Conclusion

Accurate diagnosis of FHH and differentiation from classic primary hyperparathyroidism can be challenging, however it is essential to avoid unnecessary investigations and parathyroid surgery. Genetic analysis may be helpful in establishing a diagnosis of FHH in light of the biochemical heterogeneity in this population and overlap with other causes of hypercalcaemia.
Emotional dysregulation in women with endometriosis with cyclical and non-cyclical chronic pelvic pain
Authors: Rodríguez-Lozano Dulce Carolina , Meza-Rodríguez María del Pilar , Cruz-Orozco Olivier Paul , Sánchez-Ramírez Brenda , Olguin-Ortega Andrea , Silvestri-Tomassoni José Roberto , Corona-Barsse Guillermo , Escobar-Ponce Luis Fernando , Solis-Paredes Juan Mario , Dominguez-Trejo Benjamín , Camacho-Arroyo Ignacio
Published: December 2022

Background

Endometriosis is a pathophysiological condition characterized by glands and stroma outside the uterus in regions such as the bladder, ureter, fallopian tubes, peritoneum, ovaries, and even in extra pelvic sites. One of the main clinical problems of endometriosis is chronic pelvic pain (CPP), which considerably affects the patients’ quality of life. Patients with endometriosis may, cyclically or non-cyclically (80% of cases) experience CPP. High levels of anxiety and depression have been described in patients with endometriosis related to CPP; however, this has not been evaluated in endometriosis women with different types of CPP. Therefore, the research question of this study was whether there is a difference in the emotional dysregulation due to the type of pain experienced by women with endometriosis?

Methods

This work was performed in the National Institute of Perinatology (INPer) in Mexico City from January 2019 to March 2020 and aimed to determine if there are differences in emotional dysregulation in patients with cyclical and non-cyclical CPP. 49 women from 18 to 52 years-old diagnosed with endometriosis presenting cyclical and non-cyclical CPP answered several batteries made up of Mini-Mental State Examination, Visual Analog Scale, Beck's Depression Inventory, State Trait-Anxiety Inventory, and Generalized Anxiety Inventory. Mann–Whitney U and Student’s t-test for independent samples to compare the difference between groups was used. Relative risk estimation was performed to determine the association between non-cyclical and cyclical CPP with probability of presenting emotional dysregulation.

Results

We observed that patients with non-cyclical CPP exhibited higher levels of depression and anxiety (trait-state and generalized anxiety) than patients with cyclical pain, p < 0.05 was considered significant. No differences were observed in pain intensity, but there was a higher probability of developing emotional dysregulation (anxiety or depression) in patients with non-cyclical CPP. No differences were observed in cognitive impairment.

Conclusions

Our data suggest that patients with non-cyclical (persistent) CPP present a higher emotional dysregulation than those with cyclical pain.
A real-world economic analysis of biologic therapies for psoriatic arthritis in Italy: results of the CHRONOS observational longitudinal study
Authors: Zagni Emanuela , Frassi Micol , Mariano Giuseppa Pagano , Fusaro Enrico , Lomater Claudia , Del Medico Patrizia , Iannone Florenzo , Foti Rosario , Limonta Massimiliano , Marchesoni Antonio , Raffeiner Bernd , Viapiana Ombretta , Grassi Walter , Grembiale Rosa Daniela , Guggino Giuliana , Mazzone Antonino , Tirri Enrico , Perricone Roberto , Sarzi Puttini Pier Carlo , De Vita Salvatore , Conti Fabrizio , Zullo Alessandro , Simoni Lucia , Fiocchi Martina , Orsenigo Roberto , Colombo Delia
Published: December 2022

Background

Psoriatic arthritis (PsA) is a chronic, immune-mediated, spondyloarthropathy characterised by musculoskeletal signs and symptoms with associated joint pain and tenderness. The average worldwide PsA prevalence is 133/100,000, while in the Italian population is 90–420/100,000.

Traditionally, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs have been used in the treatment of PsA. However, for those patients who are not adequately controlled with conventional therapies, the new biologics compounds represent a valid option. Biologic therapies have been shown to be more effective but also more expensive than conventional systemic treatments. Based on the CHRONOS study, the economic analyses presented in this paper aim to assess the annualised direct costs and the cost-per-responder of biologics in a real-world context assuming the Italian National Health System perspective.

Methods

The economic assessments were carried out on the overall cohort of patients, and on the tumour necrosis factor alpha inhibitors (TNFi) and the secukinumab subgroup, the most prescribed biologic therapies within the CHRONOS study.

Results

The annual economic impact of PsA in the overall group was €12,622, €11,725 in the secukinumab subgroup, and €12,791 in the TNFi subgroup. Biologics absorbed the main expenditure costs in the treatment of PsA accounting for about the 93% of total costs. At 6 months, secukinumab performed better in all the considered outcomes: cost-per-responder according to EULAR DAS28 and ACR50 response criteria were €12,661- €28,975, respectively, while they were €13,356 - €33,368 in the overall cohort and €13,138 - €35,166 in the TNFi subgroup. At 12 months secukinumab remained the subgroup with the lowest cost-per-responder ratio in EULAR DAS28 and ACR50 response criteria, while TNFi subgroup was the lowest one considered the ACR20.

Conclusion

Despite some potential methodological limitations, our cost-per-response analysis provides physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.
Echolocating bats rapidly adjust their mouth gape to control spatial acquisition when scanning a target
Authors: Eitan Ofri , Taub Mor , Boonman Arjan , Zviran Amir , Tourbabin Vladimir , Weiss Anthony J. , Yovel Yossi
Published: December 2022

Background

As well known to any photographer, controlling the “field of view” offers an extremely powerful mechanism by which to adjust target acquisition. Only a few natural sensory systems can actively control their field of view (e.g., dolphins, whales, and bats). Bats are known for their active sensing abilities and modify their echolocation signals by actively controlling their spectral and temporal characteristics. Less is known about bats’ ability to actively modify their bio-sonar field of view.

Results

We show that Pipistrellus kuhlii bats rapidly narrow their sensory field of view (i.e., their bio-sonar beam) when scanning a target. On-target vertical sonar beams were twofold narrower than off-target beams. Continuous measurements of the mouth gape of free-flying bats revealed that they control their bio-sonar beam by a ~3.6 mm widening of their mouth gape: namely, bats open their mouth to narrow the beam and vice versa.

Conclusions

Bats actively and rapidly control their echolocation vertical beam width by modifying their mouth gape. We hypothesize that narrowing their vertical beam narrows the zone of ensonification when estimating the elevation of a target. In other words, bats open their mouth to improve sensory localization.
Sex-specific expression of pheromones and other signals in gravid starfish
Authors: Jönsson Mathias , Morin Marie , Wang Conan K. , Craik David J. , Degnan Sandie M. , Degnan Bernard M.
Published: December 2022

Background

Many echinoderms form seasonal aggregations prior to spawning. In some fecund species, a spawning event can lead to population outbreaks with detrimental ecosystem impacts. For instance, outbreaks of crown-of-thorns starfish (COTS), a corallivore, can destroy coral reefs. Here, we examine the gene expression in gravid male and female COTS prior to spawning in the wild, to identify genome-encoded factors that may regulate aggregation and spawning. This study is informed by a previously identified exoproteome that attracts conspecifics. To capture the natural gene expression profiles, we isolated RNAs from gravid female and male COTS immediately after they were removed from the Great Barrier Reef. 

Results

Sexually dimorphic gene expression is present in all seven somatic tissues and organs that we surveyed and in the gonads. Approximately 40% of the exoproteome transcripts are differentially expressed between sexes. Males uniquely upregulate an additional 68 secreted factors in their testes. A suite of neuropeptides in sensory organs, coelomocytes and gonads is differentially expressed between sexes, including the relaxin-like gonad-stimulating peptide and gonadotropin-releasing hormones. Female sensory tentacles—chemosensory organs at the distal tips of the starfish arms—uniquely upregulate diverse receptors and signalling molecules, including chemosensory G-protein-coupled receptors and several neuropeptides, including kisspeptin, SALMFamide and orexin.

Conclusions

Analysis of 103 tissue/organ transcriptomes from 13 wild COTS has revealed genes that are consistently differentially expressed between gravid females and males and that all tissues surveyed are sexually dimorphic at the molecular level. This finding is consistent with female and male COTS using sex-specific pheromones to regulate reproductive aggregations and synchronised spawning events. These pheromones appear to be received primarily by the sensory tentacles, which express a range of receptors and signalling molecules in a sex-specific manner. Furthermore, coelomocytes and gonads differentially express signalling and regulatory factors that control gametogenesis and spawning in other echinoderms.
Berberine increases stromal production of Wnt molecules and activates Lgr5+ stem cells to promote epithelial restitution in experimental colitis
Authors: Luo Zecheng , Li Zihao , Liang Zheng , Wang Lin , He Guanlin , Wang Dongdi , Shen Lei , Wang Zhengting , Ma Xiuying , Geng Funeng , Wang Haozhong , Liu Wenping , Liu Huijuan , Li Baojie
Published: December 2022

Background

Inflammatory bowel diseases (IBDs) are characterized by sustained inflammation and/or ulcers along the lower digestive tract, and have complications such as colorectal cancer and inflammation in other organs. The current treatments for IBDs, which affect 0.3% of the global population, mainly target immune cells and inflammatory cytokines with a success rate of less than 40%.

Results

Here we show that berberine, a natural plant product, is more effective than the frontline drug sulfasalazine in treating DSS (dextran sulfate sodium)-induced colitis in mice, and that berberine not only suppresses macrophage and granulocyte activation but also promotes epithelial restitution by activating Lgr5+ intestinal stem cells (ISCs). Mechanistically, berberine increases the expression of Wnt genes in resident mesenchymal stromal cells, an ISC niche, and inhibiting Wnt secretion diminishes the therapeutic effects of berberine. We further show that berberine controls the expression of many circadian rhythm genes in stromal cells, which in turn regulate the expression of Wnt molecules.

Conclusions

Our findings suggest that berberine acts on the resident stromal cells and ISCs to promote epithelial repair in experimental colitis and that Wnt-β-Catenin signaling may be a potential target for colitis treatment.
Contraceptive use and contraceptive counselling interventions for women of reproductive age with cancer: a systematic review and meta-analysis
Authors: Harris Melissa L. , Feyissa Tesfaye R. , Bowden Nikola A. , Gemzell-Danielsson Kristina , Loxton Deborah
Published: December 2022

Background

A lack of clarity exists regarding contraceptive uptake and counselling among women with cancer, despite these women having unique family planning needs. This study aimed to systematically review the available literature and produce an overall summary estimate of contraceptive use and counselling among women with cancer across the cancer care continuum.

Methods

A systematic search of articles reporting on contraceptive counselling and/or contraceptive use among women of reproductive age (15–49 years) with cancer across the cancer care continuum (e.g. diagnosis, treatment, survivorship) was conducted in MEDLINE, Embase, CINAHL, Maternity and Infant Care and Cochrane Library. Two independent reviewers conducted the data screening, data extraction and risk of bias assessment. Qualitative synthesis and meta-analyses were conducted to summarise the key findings.

Results

We included 21 articles involving 3835 participants in this review. Studies varied according to the cancer population and time along the cancer care continuum it was assessed. Of the studies that reported the overall contraceptive prevalence among women diagnosed with cancer (n = 8), contraceptive use ranged from 25 to 92%. Of the four studies that focused on cancer survivors, the contraceptive prevalence ranged from 47 to 84%. When the prevalence of these studies was pooled, a crude summary prevalence of 64% (62% among women with cancer versus 68% among cancer survivors) was found. The rate of contraceptive counselling was assessed in ten studies. A pooled prevalence of 50% (44% among women with cancer versus 58% among cancer survivors) was found, with the prevalence ranging from 12 to 78% among individual studies depending on the point in the cancer care continuum that it was provided. When contraceptive counselling was provided, it was found to significantly increase contraceptive use although biases were identified in its application.

Conclusions

Contraceptive counselling interventions as part of standard cancer care have the potential to not only empower women with cancer and cancer survivors to make informed choices regarding their reproductive health but also provide the ability to plan future pregnancies for times of better health.
Construction of a ferroptosis-related signature based on seven lncRNAs for prognosis and immune landscape in clear cell renal cell carcinoma
Authors: Wei Shi-Yao , Feng Bei , Bi Min , Guo Hai-Ying , Ning Shang-Wei , Cui Rui
Published: December 2022

Background

Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are involved in regulating tumor cell ferroptosis. However, prognostic signatures based on ferroptosis-related lncRNAs (FRLs) and their relationship to the immune microenvironment have not been comprehensively explored in clear cell renal cell carcinoma (ccRCC).

Methods

In the present study, the expression profiles of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database; 459 patient specimens and 69 adjacent normal tissues were randomly separated into training or validation cohorts at a 7:3 ratio. We identified 7 FRLs that constitute a prognostic signature according to the differential analysis, correlation analysis, univariate regression, and least absolute shrinkage and selection operator (LASSO) Cox analysis. To identify the independence of risk score as a prognostic factor, univariate and multivariate regression analyses were also performed. Furthermore, CIBERSORT was conducted to analyze the immune infiltration of patients in the high-risk and low-risk groups. Subsequently, the differential expression of immune checkpoint and m6A genes was analyzed in the two risk groups.

Results

A 7-FRLs prognostic signature of ccRCC was developed to distinguish patients into high-risk and low-risk groups with significant survival differences. This signature has great prognostic performance, with the area under the curve (AUC) for 1, 3, and 5 years of 0.713, 0.700, 0.726 in the training set and 0.727, 0.667, and 0.736 in the testing set, respectively. Moreover, this signature was significantly associated with immune infiltration. Correlation analysis showed that risk score was positively correlated with regulatory T cells (Tregs), activated CD4 memory T cells, CD8 T cells and follicular helper T cells, whereas it was inversely correlated with monocytes and M2 macrophages. In addition, the expression of fourteen immune checkpoint genes and nine m6A-related genes varied significantly between the two risk groups.

Conclusion

We established a novel FRLs-based prognostic signature for patients with ccRCC, containing seven lncRNAs with precise predictive performance. The FRLs prognostic signature may play a significant role in antitumor immunity and provide a promising idea for individualized targeted therapy for patients with ccRCC.
Long noncoding RNA HOTAIR facilitates pulmonary vascular endothelial cell apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in COPD
Authors: Dai Zhongshang , Liu Xiangming , Zeng Huihui , Chen Yan
Published: December 2022

Background

To study the regulatory effect of Long non-coding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) on pulmonary vascular endothelial cell (HPVEC) apoptosis and determine whether the HOTAIR facilitate HPVEC apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in chronic obstructive pulmonary disease (COPD).

Methods

LncRNA array was used to measure the differentially expressed lncRNAs in COPD and non-COPD lung tissues. Expression of HOTAIR in COPD patient lungs and cigarette smoke extract (CSE)-induced HPVEC was assessed by qRT-PCR. The location of HOTAIR was determined in COPD patient lungs and HPVEC by RNA in situ hybridization (RNA-ISH). The emphysema mouse model and HOTAIR knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vectors instillation. The dysregulation of DNA methyltransferase enzyme 1 (DNMT1), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cleaved-caspase 3 protein expression were detected by Western blotting. HOTAIR, DNMT1, Bcl-2 and Bax mRNA expression were measured by quantitative real-time polymerase chain reaction. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays were used to assess apoptotic ratio in mice and CSE-induced HPVEC. Methylation-specific PCR (MSP) assay was conducted to observe the alterations in the methylation of the Bcl-2 promoter in specimens. RNA pull-down assay was used for analysis of the correlation between HOTAIR and DNMT1.

Results

The expression levels of the HOTAIR were up-regulated in COPD patient lungs and CSE-induced HPVEC. HPVEC apoptosis with down-regulated Bcl-2 expression, increased promoter methylation, DNMT1, Bax and Cleaved-caspase 3 expression was found in emphysema mouse model and CSE-induced HPVEC. Knockdown HOTAIR can attenuate cell apoptosis and emphysema via DNMT1 mediated hypermethylation of Bcl-2 promoter in mice. In vitro, HOTAIR can aggravate the apoptosis of CSE-exposed HPVEC. DNMT1 was a target of HOTAIR and had a positive correlation with HOTAIR.

Conclusion

HOTAIR facilitates HPVEC apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in COPD, and attenuating the expression of HOTAIR may be a new therapy to prevent COPD.