bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Italian registry for patients with Prader–Willi syndrome
Authors: Salvatore Marco , Torreri Paola , Grugni Graziano , Rocchetti Adele , Maghnie Mohamad , Patti Giuseppa , Crinò Antonino , Elia Maurizio , Greco Donatella , Romano Corrado , Franzese Adriana , Mozzillo Enza , Colao Annamaria , Pugliese Gabriella , Pagotto Uberto , Lo Preiato Valentina , Scarano Emanuela , Schiavariello Concetta , Tornese Gianluca , Fintini Danilo , Bocchini Sarah , Osimani Sara , De Sanctis Luisa , Sacco Michele , Rutigliano Irene , Delvecchio Maurizio , Faienza Maria Felicia , Wasniewska Malgorzata , Corica Domenico , Stagi Stefano , Guazzarotti Laura , Maffei Pietro , Dassie Francesca , Taruscio Domenica 
Published: February 2023

Abstract
Background
Prader–Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients’ care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results.

Materials and methods
The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality.

Results
A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019–2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment.

Conclusions
The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.
The Alzheimer’s disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130
Authors: Müller Stephan A. , Shmueli Merav D. , Feng Xiao , Tüshaus Johanna , Schumacher Neele , Clark Ryan , Smith Brad E. , Chi An , Rose-John Stefan , Kennedy Matthew E. , Lichtenthaler Stefan F. 
Published: February 2023

Abstract
Background
The protease BACE1 is a major drug target for Alzheimer’s disease, but chronic BACE1 inhibition is associated with non-progressive cognitive worsening that may be caused by modulation of unknown physiological BACE1 substrates.

Methods
To identify in vivo-relevant BACE1 substrates, we applied pharmacoproteomics to non-human-primate cerebrospinal fluid (CSF) after acute treatment with BACE inhibitors.

Results
Besides SEZ6, the strongest, dose-dependent reduction was observed for the pro-inflammatory cytokine receptor gp130/IL6ST, which we establish as an in vivo BACE1 substrate. Gp130 was also reduced in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. Mechanistically, we demonstrate that BACE1 directly cleaves gp130, thereby attenuating membrane-bound gp130 and increasing soluble gp130 abundance and controlling gp130 function in neuronal IL-6 signaling and neuronal survival upon growth-factor withdrawal.

Conclusion
BACE1 is a new modulator of gp130 function. The BACE1-cleaved, soluble gp130 may serve as a pharmacodynamic BACE1 activity marker to reduce the occurrence of side effects of chronic BACE1 inhibition in humans.

Graphical abstract
The perceived impact of Covid-19 pandemic on the children with cerebral palsy: the parents’ perspective explored within the “6-F words” framework
Authors: Pizzighello Silvia , Uliana Marianna , Martinuzzi Michela , Vascello Matteo G. F. , Cipriani Martina , Breda Martina , De Polo Gianni , Martinuzzi Andrea 
Published: February 2023

Abstract
Background
In 2020 the world faced the spread of the coronavirus infection disease (Covid-19). This was a general public health emergency but many people with disabilities might have been particularly affected.

Objective
This paper aims to investigate the impact of the Covid-19 pandemic on children with Cerebral Palsy (CP) and their families.

Methods
110 parents of children with CP (aged 2 to 19) who completed a questionnaire were included. These children were under the care of one of the Italian Children Rehabilitation Centers. Socio-demographic and clinical information about patients and their families were collected. In addition, difficulties on adopting protective measures and in respecting lockdown rules by children were explored. We adopted the ICF (International Classification of Functioning, Disability and Health) framework to create multiple choice questions. Descriptive statistics were reported and logistic regression analyses were run in order to identify the predictors of perceived impairment in motor, speech, manual and behavioral abilities.

Results
Daily activities of children, as well as rehabilitation and fitness sessions, underwent a change during the pandemic. Spending more time with family due to lockdown measures, has had, in some cases a positive effect however there was a perceived decrease in rehabilitation support and school activities. The age range (between 7 and 12 years) and difficulty in respecting rules emerged as significant predictors of the perceived impairment due to Covid-19 pandemic.

Conclusions
The pandemic has had different impacts on children and their families on the basis of children’s characteristics. Rehabilitation activities during a hypothetic lockdown should consider these characteristics.
A multi-center, open-label, randomized study to explore efficacy and safety of baricitinib in active primary Sjogren’s syndrome patients
Authors: Bai Wei , Yang Fan , Xu Huji , Wei Wei , Li Hongbin , Zhang Liyun , Zhao Yi , Shi Xiaofei , Zhang Yan , Zeng Xiaofeng , Leng Xiaomei 
Published: February 2023

Abstract
Background
Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease involving multiple organ systems. The Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway is a key pathway involving the pathogenesis of pSS. Baricitinib, a selective JAK1 and JAK2 inhibitor, has been approved for treatment of active rheumatoid arthritis and reported in treatment of some other autoimmune diseases including systemic lupus erythematosus. We have found that baricitinib might be effective and safe in pSS in a pilot study. However, there is no published clinical evidence of baricitinib in pSS. Hence, we conducted this randomized study to further explore the efficacy and safety of baricitinib in pSS.

Methods
This is a multi-center, prospective, open-label, randomized study to compare the efficacy of baricitinib + hydroxychloroquine (HCQ) with HCQ alone in pSS patients. We plan to involve 87 active pSS patients with European League Against Rheumatism pSS disease activity index (ESSDAI) ≥ 5 from eight different tertiary centers in China. Patients will be randomized (2:1) to receive baricitinib 4 mg per day + HCQ 400 mg per day or HCQ 400 mg per day alone. We will switch HCQ to baricitinib + HCQ if the patient in the latter group has no ESSDAI response at week 12. The final evaluation will be at week 24. The primary endpoint is the percentage of ESSDAI response, or minimal clinically important improvement (MCII), which was defined as an improvement of ESSDAI at least three points at week 12. The secondary endpoints include EULAR pSS patient-reported index (ESSPRI) response, change of Physician’s Global Assessment (PGA) score, serological activity parameters, salivary gland function test, and focus score on labial salivary gland biopsy.

Discussion
This is the first randomized controlled study to evaluate the clinical efficacy and safety of baricitinib in pSS. We hope that the result of this study can provide more reliable evidence of the efficacy and safety of baricitinib in pSS.

Trial registration
ClinicalTrials.gov NCT05016297. Registered on 19 Aug 2021.
The Skin Antiseptic agents at Vaginal dElivery (SAVE) trial: study protocol for a randomized controlled trial
Authors: Jung Young Mi , Lee Seung Mi , Kim So Yeon , Chung Jin Hoon , Won Hye-Sung , Lee Kyung A , Park Mi Hye , Cho Geum Joon , Oh Min-Jeong , Choi Eun Saem , Ahn Ki Hoon , Hong Soon-Cheol , Sung Ji-Hee , Roh Cheong-Rae , Kim Sun Min , Kim Byoung Jae , Kim Hyeon Ji , Oh Kyung Joon , Hong Subeen , Park In Yang , Park Joong Shin 
Published: February 2023

Abstract
Background
Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery.

Methods
In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions.

Discussion
This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery.

Trial registration
ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 2021
Modified prolonged exposure therapy as Early Intervention after Rape (The EIR-study): study protocol for a multicenter randomized add-on superiority trial
Authors: Haugen Tina , Halvorsen Joar Øveraas , Friborg Oddgeir , Simpson Melanie Rae , Mork Paul Jarle , Mikkelsen Gustav , Elklit Ask , Rothbaum Barbara O. , Schei Berit , Hagemann Cecilie 
Published: February 2023

Abstract
Background
Sexual assault and rape are the traumatic life events with the highest probability for posttraumatic stress disorder (PTSD), which can have devastating consequences for those afflicted by the condition. Studies indicate that modified prolonged exposure (mPE) therapy may be effective in preventing the development of PTSD in recently traumatized individuals, and especially for people who have experienced sexual assault. If a brief, manualized early intervention can prevent or reduce post-traumatic symptoms in women who have recently experienced rape, healthcare services targeted for these populations (i.e., sexual assault centers, SACs) should consider implementing such interventions as part of routine care.

Methods/design
This is a multicenter randomized controlled add-on superiority trial that enrolls patients attending sexual assault centers within 72 h after rape or attempted rape. The objective is to assess whether mPE shortly after rape can prevent the development of post-traumatic stress symptoms. Patients will be randomized to either mPE plus treatment as usual (TAU) or TAU alone. The primary outcome is the development of post-traumatic stress symptoms 3 months after trauma. Secondary outcomes will be symptoms of depression, sleep difficulties, pelvic floor hyperactivity, and sexual dysfunction. The first 22 subjects will constitute an internal pilot trial to test acceptance of the intervention and feasibility of the assessment battery.

Discussion
This study will guide further research and clinical initiatives for implementing strategies for preventing post-traumatic stress symptoms after rape and provide new knowledge about which women may benefit the most from such initiatives and for revising existing treatment guidelines within this area.

Trial registration
ClinicalTrials.gov NCT05489133. Registered on 3 August 2022
Intratympanic membrane cholesteatoma after traumatic tympanic membrane perforation: a case report
Authors: Jeong Junhui , Choi Hyun Seung 
Published: February 2023

Abstract
Background
Intratympanic membrane cholesteatoma presents as an asymptomatic, white, round mass on the tympanic membrane, and is usually detected incidentally in children.

Case presentation
A 12-year-old Korean boy visited our otorhinolaryngology clinic for a whitish mass on the right tympanic membrane. He had a history of traumatic tympanic membrane perforation in the right ear that had occurred 1 year prior, which had healed well with a paper patch placement. The mass was completely removed under local anesthesia during surgery with a microscope. The mass was on the outer epithelial layer of the right tympanic membrane and did not invade the middle fibrous and inner mucosal layers. Cholesteatoma was diagnosed on the basis of histopathology.

Conclusion
Intratympanic membrane cholesteatoma may not induce symptoms or invade the middle ear because it can grow outwards into the external auditory canal. However, intratympanic membrane cholesteatoma can grow over time, and then after growth, it can compress the tympanic membrane and advance into the middle ear, which can cause symptoms such as hearing loss. Intratympanic membrane cholesteatoma in children should be carefully evaluated and followed, and surgical removal should be considered, even for asymptomatic cases, to minimize potential damage and hearing loss.
Thrombocytopenia, anasarca, and renal insufficiency as severe and rare complications of Hodgkin lymphoma: a case report
Authors: Kikuchi Tatsuya , Tanaka Yoshinori , Ichimura Kouichi , Okada Hiroyuki , Okamoto Ryoichi 
Published: February 2023

Abstract
Background
Patients with Hodgkin lymphoma exhibit various clinical presentations. Needle biopsy of the lymph nodes is a minimally invasive procedure and a useful diagnostic method for malignant lymphomas. However, at times it is difficult to differentiate malignant lymphomas from reactive lymph node changes using a small amount of biopsy material.

Case presentation
A 77-year-old Japanese man was referred to the emergency department of our hospital owing to high fever and disturbance of consciousness. We diagnosed sepsis due to an acute biliary tract infection because he presented with Charcot’s triad—fever, jaundice, and right-sided abdominal pain. However, he did not respond well to antimicrobial therapy and his high fever persisted. Considering the swelling of the right cervical, mediastinal, and intraperitoneal lymph nodes and splenomegaly detected on computed tomography, a differential diagnosis of malignant lymphoma was needed. Hence, we performed a needle biopsy of the right cervical lymph node; however, the amount of sample obtained was insufficient in establishing a definitive diagnosis of malignant lymphoma. Furthermore, during hospitalization, the patient developed thrombocytopenia, anasarca, and renal insufficiency. These symptoms seemed to be the typical signs of the thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, and organomegaly syndrome. Next, an external incisional mass biopsy of the right cervical lymph node was performed, which helped identify Hodgkin and Reed–Sternberg cells. Collectively, we established a definitive diagnosis of Hodgkin lymphoma with lymphoma-associated hemophagocytic syndrome.

Conclusions
This case highlights the importance of performing an external incisional mass biopsy of the lymph nodes for the early diagnosis and treatment, if malignant lymphoma is strongly suspected.
Cell cycle regulators and bone: development and regeneration
Authors: Shaikh Alisha , Wesner Austin A. , Abuhattab Mohanad , Kutty Raman G. , Premnath Priyatha 
Published: February 2023

AbstractCell cycle regulators act as inhibitors or activators to prevent cancerogenesis. It has also been established that they can play an active role in differentiation, apoptosis, senescence, and other cell processes. Emerging evidence has demonstrated a role for cell cycle regulators in bone healing/development cascade. We demonstrated that deletion of p21, a cell cycle regulator acting at the G1/S transition enhanced bone repair capacity after a burr-hole injury in the proximal tibia of mice. Similarly, another study has shown that inhibition of p27 can increase bone mineral density and bone formation. Here, we provide a concise review of cell cycle regulators that influence cells like osteoblasts, osteoclasts, and chondrocytes, during development and/or healing of bone. It is imperative to understand the regulatory processes that govern cell cycle during bone healing and development as this will pave the way to develop novel therapies to improve bone healing after injury in instances of aged or osteoporotic fractures.
Excellent survival of pathological N0 small cell lung cancer patients following surgery
Authors: Fu Zichen , Li Di , Deng Chaoqiang , Zhang Jingshun , Bai Jinsong , Li Yuan , Chen Haiquan , Zhang Yang 
Published: February 2023

Abstract
Background
Current clinical guidelines recommend surgery only for cT1-2N0M0 small cell lung cancer (SCLC) patients. In light of recent studies, the role of surgery in the treatment of SCLC needs to be reconsidered.

Methods
We reviewed all SCLC patients who underwent surgery from November 2006 to April 2021. Clinicopathological characteristics were retrospectively collected from medical records. Survival analysis was performed by the Kaplan–Meier method. Independent prognostic factors were evaluated by Cox proportional hazard model.

Results
196 SCLC patients undergoing surgical resection were enrolled. The 5-year overall survival for the entire cohort was 49.0% (95% CI: 40.1–58.5%). PN0 patients had significantly superior survival to pN1–2 patients (p < 0.001). The 5-year survival rate of pN0 and pN1–2 patients were 65.5% (95% CI: 54.0–80.8%) and 35.1% (95% CI: 23.3–46.6%), respectively. Multivariate analysis revealed that smoking, older age, and advanced pathological T and N stages were independently associated with poor prognosis. Subgroup analyses demonstrated similar survival among pN0 SCLC patients regardless of pathological T stages (p = 0.416). Furthermore, multivariate analysis showed factors, including age, smoking history, type of surgery, and range of resection, were not independently prognostic factors for the pN0 SCLC patients.

Conclusion
Pathological N0 stage SCLC patients have significantly superior survival to pN1–2 patients, regardless of features, including T stage. Thorough preoperative evaluation should be applied to estimate the status of lymph node involvement to achieve better selection of patients who might be candidate for surgery. Studies with larger cohort might help verify the benefit of surgery, especially for T3/4 patients.
Reimagining eating disorder spaces: a qualitative study exploring Māori experiences of accessing treatment for eating disorders in Aotearoa New Zealand
Authors: Clark Mau Te Rangimarie , Manuel Jenni , Lacey Cameron , Pitama Suzanne , Cunningham Ruth , Jordan Jennifer 
Published: February 2023

Abstract
Background
Health, illness, and the body are conceptualized within the cultural context of a society. The values and belief systems of a society, including media portrayals, shape how health and illness present. Traditionally, Western portrayals of eating disorders have been prioritized over and above Indigenous realities. This paper explores the lived experiences of Māori with eating disorders and their whānau (family/support system) to identify the enablers and barriers to accessing specialist services for eating disorders in New Zealand.

Method
Kaupapa Māori research methodology was used to ensure the research supported Māori health advancement. Fifteen semi-structured interviews were completed with Māori participants including; those with an eating disorder diagnosis (anorexia nervosa, bulimia nervosa, and binge eating disorder), and/or their whānau. Structural, descriptive, and pattern coding was undertaken within the thematic analysis. Low’s spatializing culture framework was used to interpret the findings.

Results
Two overarching themes identified systemic and social barriers to accessing treatment for Māori with eating disorders. The first theme, was space, that described the material culture within eating disorder settings. This theme critiqued eating disorder services, including idiosyncratic use of assessment methods, inaccessible service locations, and the limited number of beds available in specialist mental health services. The second theme, place, referred to the meaning given to social interactions created within space. Participants critiqued the privileging of non-Māori experiences, and how this makes a place and space of exclusion for Māori and their whānau in eating disorder services in New Zealand. Other barriers included shame and stigma, while enablers included family support and self-advocacy.

Conclusion
More education is needed for those working in the space of primary health settings about the diversity of those with eating disorders to enable them to look beyond the stereotype of what an eating disorder looks like, and to take seriously the concerns of whaiora and whānau who present with disordered eating concerns. There is also a need for thorough assessment and early referral for eating disorder treatment to ensure the benefits of early intervention are enabled for Māori. Attention given to these findings will ensure a place for Māori in specialist eating disorder services in New Zealand.

Graphical Abstract