bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment patterns among children and adolescents with attention-deficit/hyperactivity disorder in the United States – a retrospective claims analysis
Authors: Schein Jeff , Childress Ann , Adams Julie , Gagnon-Sanschagrin Patrick , Maitland Jessica , Qu Wendi , Cloutier Martin , Guérin Annie 
Published: August 2022

Abstract
Background
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder affecting approximately 10.0% of children and 6.5% of adolescents in the United States (US). A comprehensive assessment of the current treatment landscape is warranted to highlight potential unmet needs of children and adolescents with ADHD. Therefore, this study described treatment patterns and healthcare costs among commercially insured children and adolescents with ADHD in the US.

Methods
Children and adolescents with ADHD initiating pharmacological treatment indicated for ADHD were identified from IBM MarketScan Commercial Database (2014–2018). A treatment sequence algorithm was used to examine treatment patterns, including discontinuation (≥ 180 days following the last day of supply of any ADHD treatment), switch, add-on, and drop (discontinuation of an agent in combination therapy), during the 12-month study period following the index date (i.e., first observed ADHD treatment). Total adjusted annual healthcare costs were compared between patients with and without treatment changes.

Results
Among 49,756 children and 29,093 adolescents included, mean age was 9 and 15 years, respectively, and 31% and 38% were female. As the first treatment regimen observed, 92% of both children and adolescents initiated a stimulant and 11% initiated combination therapy. Over half of the population had a treatment change over 12 months—59% of children and 68% of adolescents. Treatment discontinuation over 12 months was common in both populations—21% of children and 36% of adolescents discontinued treatment. Healthcare costs increased with the number of treatment changes observed; children and adolescents with treatment changes (i.e., 1, 2, or ≥ 3) incurred an incremental annual cost of up to $1,443 and $2,705, respectively, compared to those without a treatment change (p < 0.001). Costs were largely driven by outpatient visits.

Conclusions
Over a 12-month period, treatment changes were commonly observed and were associated with excess costs, highlighting the unmet treatment needs of children and adolescents with ADHD in the US.
Preoperative prediction of sagittal imbalance in kyphosis secondary to ankylosing spondylitis after one-level three-column osteotomy
Authors: Luo Jianzhou , Yang Kai , Yang Zili , Chen Jiayi , Huang Zhengji , Luo Zhenjuan , Tao Huiren , Duan Chunguang , Wu Tailin 
Published: August 2022

Abstract
Background
This study aimed to determine preoperative predictors for sagittal imbalance in kyphosis secondary to ankylosing spondylitis (AS) after one-level three-column osteotomy.

Methods
A total of 55 patients with AS who underwent one-level three-column osteotomy were enrolled. The patients were divided into two groups according to sagittal vertical axis (SVA) value at the final follow-up (group A: SVA > 5 cm; group B: SVA ≤ 5 cm). The radiographic measures included global kyphosis, lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sacral slope, T1 pelvic angle (TPA), SVA, osteotomized vertebral angle and PI and LL mismatch (PI − LL). Postoperative clinical outcomes were evaluated using Scoliosis Research Society-22 questionnaire (SRS-22) and Oswestry Disability Index (ODI).

Results
Fifty-five AS patients had an average follow-up of 30.6 ± 10.2 months (range 24–84 months). Group A had larger preoperative and postoperative LL, PT, PI − LL, TPA and SVA values compared with group B (P < 0.05), and no significant differences were found in ODI and SRS-22 scores between the two groups (P > 0.05). Preoperative LL, PT, PI − LL, TPA, and SVA values were positively correlated with the follow-up SVA value (P < 0.05). Among them, TPA > 40.9°, PI − LL > 32.5° and SVA > 13.7 cm were the top three predictors with the best accuracy to predict sagittal imbalance. Immediate postoperative SVA value of ≤ 7.4 cm was a key factor in reducing the risk of sagittal imbalance during follow-up.

Conclusions
Preoperative TPA > 40.9°, PI − LL > 32.5° and SVA > 13.7 cm could predict sagittal imbalance in AS kyphosis after one-level three-column osteotomy, and additional osteotomies were recommended for this condition. Immediate postoperative SVA ≤ 7.4 cm was an optimal indicator for preventing sagittal imbalance.

Level of evidence
IV.
High burden of invasive and non-invasive cancer among women aged 20–49 years: the situation in Geneva, Switzerland
Authors: Rapiti Elisabetta , Fournier Evelyne , Schaffar Robin 
Published: August 2022

Abstract
Background
The pattern of cancer among young adults aged 20–49 years is different than that observed in other age groups, most notably women present higher rates than those observed among men. Estimations of the burden of cancer disease among women of this age group, however, rarely include both invasive and non-invasive disease.

Methods
We calculated incidence rates of invasive and non-invasive cancers for women and men aged 20–49 years and by cancer site for the period 2014–2018 in the canton of Geneva, Switzerland using data from the population-based cancer registry.

Results
Between 2014 and 2018, the incidence rates of invasive and non-invasive cancers among women were 177.6/100,000 and 166.4/100,000, respectively. The rates among men of the same age were 110.6/100,000 and 31.8/100,000, respectively. Just three cancers, breast, thyroid and melanoma accounted for 70% of all invasive cancers among women. In situ cervical cancer represented over 70% of non-invasive disease.

Conclusion
Cancer among women aged 20–49 years is quite frequent. This is primarily a result of increasing risk, increased diagnosis or both and highlights the need for better primary prevention strategies, personalized risk assessment and tailored screening, as well as increased awareness of women and health professionals about health risks in young adults.
Empathy as a learning objective in medical education: using phenomenology of learning theory to explore medical students’ learning processes
Authors: Assing Hvidt Elisabeth , Ulsø Anne , Thorngreen Cecilie Valentin , Søndergaard Jens , Andersen Christina Maar 
Published: August 2022

Abstract
Background
Clinical empathy has been associated with a range of positive patient- and clinician outcomes. Educating medical students to become empathic physicians has in recent years become a clearly pronounced learning objective in medical education in many countries worldwide. Research knowledge about how medical students experience the learning processes conveyed by empathy-enhancing educational interventions is lacking. Our study aimed to explore Danish medical students’ perspectives on which experiences allowed learning processes to take place in relation to empathy and empathic communication with patients.

Methods
We conducted a qualitative research study, involving semi-structured interviews with twenty-three Danish medical students across years of curriculum and universities. Braun and Clarke’s reflexive thematic analysis (RTA) guided the analytical process, moving on a continuum from inductive to deductive, theoretical approaches. Key concepts in regard to learning processes deriving from Amadeo Giorgi’s learning theory were applied to analyse the data.

Results
Learning processes in relation to clinical empathy occured: 1. when theoretical knowledge about empathy became embodied and contextualied within a clinical context 2. through interpersonal interactions, e.g., with peers, faculty members and clinicians, that conveyed behavior-mobilizing positive and negative affect and 3. when new learning discoveries in 2. and 3. were appropriated as a personalized and adequate behavior that transcends the situational level.

Conclusion
Rather than being an immediate product of knowledge transmission, skill acquisition or training, learning clinical empathy is experienced as a dynamic, temporal process embedded in a daily clinical lifeworld of becoming an increasingly human professional.
Perceptions, practices and barriers to reporting of adverse drug reactions among HIV infected patients and their doctors in 3 public sector hospitals of the Ethekwini Metropolitan, Kwa-Zulu Natal: a cross sectional and retrospective analysis
Authors: Zondi Sindiswa , Naidoo Panjasaram 
Published: August 2022

Abstract
Background
Adverse drug reactions (ADRs) remain a global public health concern. Pharmacovigilance practises are essential in ensuring patients safety and post drug marketing surveillance. This study aimed to describe practices, perceptions and barriers towards ADR reporting practices amongst People Living with HIV/AIDS (PLWHA), who are on Highly Active Anti-Retroviral Therapy (HAART) and their doctors.

Methods
The study took place at 3 public sector hospitals. The first phase of the study was a quantitative cross-sectional study using a closed ended questionnaire that was given to PLWHA. Phase two was a retrospective analysis of these patients’ medical files, whilst phase 3 included a descriptive statistics to determine the frequencies and percentages for variables such as ADR reporting practices by doctors.

Results
Spontaneous reporting, was evident with 202 patients (48%) indicating that they reported experiencing ADRs to their doctors. Ten doctors (77%) indicated that they received PV training. Eight (62%) doctors indicated that the completed ADR reporting forms were submitted to the pharmacy manager in the hospital for forwarding to the regulatory authority, with 2 (15%) indicating that they submitted directly to the South African Health Products Regulatory Authority. Four (31%) doctors stated that the system of reporting ADRs is ineffective with the majority of the doctors 12 (92%) responding that the reporting of ADRs is very important/critical. A barrier cited by 4 patients (0.9%) for non-reporting of their ADRs was transport cost. Whilst doctors' barriers included reporting being time consuming (31%), and a lack of availability of reporting forms (31%).

Conclusion
Patients and doctors are reporting ADRs but more education and easier reporting process should be available to strengthen the knowledge and reporting of ADRs. Doctors agree that it is critical to report ADRs. Electronic reporting should be encouraged to lessen the time it takes to report ADRs.
The trust and insurance models of healthcare purchasing in the Ayushman Bharat Pradhan Mantri Jan Arogya Yojana in India: early findings from case studies of two states
Authors: Furtado Kheya Melo , Raza Arif , Mathur Devasheesh , Vaz Nafisa , Agrawal Ruchira , Shroff Zubin Cyrus 
Published: August 2022

Abstract
Background
The Pradhan Mantri Jan Arogya Yojana (PMJAY), a publicly funded health insurance scheme for the poor in India, was launched in 2018. Early experiences of states with various purchasing arrangements can provide valuable insights for its future performance. We sought to understand the institutional agencies and performance of the trust and insurance models of purchasing with respect to; a) Provider contracting b) Claim management c) Implementation costs.

Methods
A mixed methods case study design was adopted. Two states, Uttar Pradesh (representing a trust model) and Jharkhand (representing the insurance model) were purposively selected. Data sources included document reviews, key informant interviews, quantitative scheme data from the provider empanelment and claims database, and primary data on costs. Descriptive statistics were reported for quantitative data, content analysis was used for thematic reporting of qualitative data.

Results
In both models, the state was the final authority on empanelment decisions, with no significant influence of the insurance company. Private hospitals constituted the majority of empanelled providers, with wide variations in district-wise distribution of bed capacities in both states. The urgency of completing empanelment in the early days of the scheme created the need for both states to re-review hospitals and de-empanel those not meeting requirements. Very few quality- accredited private hospitals were empaneled. The trust displayed more oversight of support agencies for claim management, longer processing times, a higher claim rejection rate and numbers of queries raised, as compared to the insurance model. Support agencies in both states faced challenges in assessing the clinical decisions of hospitals. Cost-effectiveness showed mixed results; the trust cost less than the insurance model per beneficiary enrolled, but more per claim generated.

Conclusions
Efforts are required to enable a better distribution and ensure quality of care in empanelled hospitals. The adoption of standard treatment guidelines is needed to support hospitals and implementing agencies in better claim management. The oversight of agencies through enforcement of contracts remains vital in both models. Assessing the comparative performance of trusts and insurance companies in more states at later stages of scheme implementation, would be further useful to determine their cost-effectiveness as purchasers.
The A’-helix of CYP11A1 remodels mitochondrial cristae
Authors: Rosal Karen G. , Chen Wei-Yi , Chung Bon-chu 
Published: August 2022

Abstract
Background
CYP11A1 is a protein located in the inner membrane of mitochondria catalyzing the first step of steroid synthesis. As a marker gene for steroid-producing cells, the abundance of CYP11A1 characterizes the extent of steroidogenic cell differentiation. Besides, the mitochondria of fully differentiated steroidogenic cells are specialized with tubulovesicular cristae. The participation of CYP11A1 in the change of mitochondrial structure and the differentiation of steroid-producing cells, however, has not been investigated.

Methods
We engineered nonsteroidogenic monkey kidney COS1 cells to express CYP11A1 upon doxycycline induction and examined the mitochondrial structure of these cells. We also mapped the CYP11A1 domains that confer structural changes of mitochondria. We searched for CYP11A1-interacting proteins and investigated the role of this interacting protein in shaping mitochondrial structure. Finally, we examined the effect of CYP11A1 overexpression on the amount of mitochondrial contact site and cristae organizing system.

Results
We found that CYP11A1 overexpression led to the formation of tubulovesicular cristae in mitochondria. We also identified the A’-helix located at amino acid #57–68 to be sufficient for membrane insertion and crista remodeling. We identified heat shock protein 60 (Hsp60) as the CYP11A1-interacting protein and showed that Hsp60 is required for CYP11A1 accumulation and crista remodeling. Finally, we found that the small MIC10 subcomplex of the mitochondrial contact site and cristae organizing system was reduced when CYP11A1 was overexpressed.

Conclusions
CYP11A1 participates in the formation of tubulovesicular cristae in the mitochondria of steroidogenic cells. Its A’-helix is sufficient for the formation of tubulovesicular cristae and for protein integration into the membrane. CYP11A1 interacts with Hsp60, which is required for CYP11A1 accumulation. The accumulation of CYP11A1 leads to the reduction of MIC10 complex and changes mitochondrial structure.
Elevated cholesteryl ester transfer and phospholipid transfer proteins aggravated psoriasis in imiquimod-induced mouse models
Authors: Chen Jun , Qi Haihua , Liu Lijun , Niu Yandong , Yu Shuping , Qin Shucun , He Lei 
Published: August 2022

Abstract
Background
Psoriasis is a chronic inflammatory skin disorder related to dyslipidemia, with decreased high-density lipoprotein (HDL). Various cell types express phospholipid transfer protein (PLTP) as well as cholesteryl ester transfer protein (CETP). Their elevated levels among transgenic (Tg) mice led to reduced HDL and a higher risk of atherosclerosis (AS). This study examined whether elevated CETP and PLTP could aggravate psoriasis in a psoriasis vulgaris mouse model.

Methods
The back skins of CETP-Tg, PLTP-Tg, and C57BL/6 male mice, aged six to 8 weeks, were shaved for imiquimod cream (IMQ) (5%) treatment for five consecutive days. The clinical pathological parameters were rated independently using the modified target lesion psoriasis severity score. The skin sections stained with hematoxylin-eosin were scored by the Baker score. Epidermal thickening and differentiation and inflammatory factor infiltration were determined by immunohistochemistry. Inflammatory cytokine levels were measured using quantitative reverse transcription-polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA) kits. This work employed SPSS Statistics Version to conduct statistical analyses.

Results
In this study, CETP-Tg and PLTP-Tg mice had higher clinical and histological scores than wild-type (WT) mice. Immunohistochemistry of the epidermis and dermis revealed a high proportion of proliferating cell nuclear antigen (PCNA) positivity within psoriatic skin lesions of CETP-Tg and PLTP-Tg mice compared with WT mice. Interferon-α (IFN-α), interleukin-1β (IL-1β), IL-6, IL-17A, IL-17F, IL-22, and IL-23p19 mRNA levels increased within CETP-Tg and PLTP-Tg mice compared with WT counterparts. In comparison with WT mice, plasma tumor necrosis factor-α (TNF-α) levels, rather than IL-6 levels, were increased in CETP-Tg and PLTP-Tg mice.

Conclusions
Elevated CETP and PLTP aggravate psoriasis in a imiquimod-induced mouse model.
CC-99677, a novel, oral, selective covalent MK2 inhibitor, sustainably reduces pro-inflammatory cytokine production
Authors: Gaur Rajula , Mensah Kofi A. , Stricker Jason , Adams Mary , Parton Anastasia , Cedzik Dorota , Connarn Jamie , Thomas Michael , Horan Gerald , Schafer Peter , Mair Stuart , Palmisano Maria , Ramírez-Valle Francisco 
Published: August 2022

Abstract
Background
Mitogen-activated protein kinase (MAPK)-activated protein kinase-2 (MK2) is activated downstream of p38 MAPK and regulates stability of mRNAs encoding inflammatory cytokines. CC-99677 is a novel, irreversible, covalent MK2 inhibitor under development for the treatment of ankylosing spondylitis (AS) and other inflammatory diseases. As part of a phase I clinical trial to assess safety and tolerability, we evaluated target engagement, pharmacokinetics, and pharmacodynamics of CC-99677.

Methods
The MK2 inhibitor CC-99677 was evaluated for its effect on cytokine expression in vitro in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with a definitive AS diagnosis. A novel in vitro model was developed to compare the potential for tachyphylaxis of CC-99677 and p38 inhibitors in THP-1 cells. The effect of CC-99677 on tristetraprolin (TTP) and cytokine mRNA was assessed in stimulated human monocyte-derived macrophages. In a first-in-human study, thirty-seven healthy volunteers were randomly assigned to daily oral doses of CC-99677 or placebo, and blood was collected at pre-specified time points before and after dosing. CC-99677 concentrations were assessed in the plasma, and CC-99677 binding to MK2 was evaluated in PBMCs. Ex vivo stimulation of the whole blood was conducted from participants in the first-in-human study to assess the pharmacodynamic effects.

Results
In vitro, CC-99677 inhibited tumor necrosis factor (TNF), interleukin (IL)-6, and IL-17 protein production in samples of monocytes and macrophages from AS patients and healthy volunteers via an mRNA-destabilization mechanism. In the in vitro model of tachyphylaxis, CC-99677 showed a differentiated pattern of sustained TNF protein inhibition compared with p38 inhibitors. CC-99677 reduced TTP phosphorylation and accelerated the decay of inflammatory cytokine mRNA in lipopolysaccharide-stimulated macrophages. Administration of CC-99677 to healthy volunteers was safe and well-tolerated, with linear pharmacokinetics and sustained reduction of ex vivo whole blood TNF, IL-6, and chemokine synthesis.

Conclusions
CC-99677 inhibition of MK2 is a promising approach for the treatment of inflammatory diseases and may overcome the limitations of p38 MAPK inhibition.

Trial registration
ClinicalTrials.gov NCT03554993.
Low apparent diffusion coefficient in an extracranial brain tumor: a case report
Authors: Tuan Ho Xuan , Hung Nguyen Duy , Minh Nguyen Dinh , Quang Nguyen Nhat , Duy Ngo Quang , Duc Nguyen Minh 
Published: August 2022

Abstract
Background
Medulloblastoma is well known as the most common malignant brain tumor identified in children, frequently found at an intra-axial location in the posterior cranial fossa. Extra-axial medulloblastoma is uncommon and often misdiagnosed. We believe that a thorough understanding of atypical medulloblastoma cases is important in daily practice.

Case presentation
We present the unique case of a 39-year-old woman of Asian descent who suffered from headaches and right-sided hearing impairment. A right extra-axial medulloblastoma with an extremely low apparent diffusion coefficient of 0.404 × 10−3 mm2/second was detected on magnetic resonance imaging. The initial diagnosis suggested schwannoma or hemangioblastoma. However, the postoperative histopathologic findings indicated medulloblastoma (World Health Organization grade IV). Pre- and postoperative magnetic resonance imaging revealed no drop metastasis, but adjuvant radiation therapy was still required as a standard treatment therapy

Conclusions
Extra-axial medulloblastoma is an uncommon tumor that is often mistaken for other cerebellopontine angle neoplasms. We describe a rare example of extra-axial medulloblastoma, characterized by a low apparent diffusion coefficient. When evaluating an atypical cerebellopontine angle neoplasm, the apparent diffusion coefficient should be considered a relevant indicator.
Mental distress among university students in the Eastern Cape Province, South Africa
Authors: Mutinta Given 
Published: August 2022

Abstract
Introduction
Mental distress is a global health concern. Studies show that the prevalence of mental distress is higher in students’ population than in the general population. Therefore, there is need to understand the extent and factors associated with mental distress among students to help policymakers and practitioners in South Africa.

Aim of the study
The study was designed to investigate into the prevalence and factors associated with mental distress among students at universities in the Eastern Cape Province, South Africa.

Methods
A cross-sectional study was conducted among students from four universities in the Eastern Cape Province. The data were collected from 844 students using an online self-reporting questionnaire-20 to assess mental distress of students. Multivariable logistic regression modelling determined the association between socio-demographic and psychosocial factors with students’ mental distress.

Findings
The prevalence of mental distress among students was 53.3% (95% CI 47.0%, 58.1%). Female students were more prone to mental distress than male students ([AOR]: 4.67; 95% CI 2.82, 7.72, P = 0.001). Field of study ([AOR]: 3.9; 95% CI 1.74, 5.50, P = 0.010), year of study ([AOR]: 4.29; 95% CI 0.86, 21.46, P = 0.002), academic workload ([AOR]: 4.66; 95% CI 2.81, 7.71, P = 0.003), poor sleep quality ([AOR]: 2.24; 95% CI 1.13, 3.67, P = 0.010) and using cannabis ([AOR]: 3.10; 95% CI 1.755, 5.51, P = 0.020) were other factors significantly correlated with students’ mental distress.

Conclusions and recommendations
The study found the level of mental distress to be higher among students than what is reported in most of the previous studies on the student population in South Africa. Being a female student, a user of cannabis, and field of study, academic workload and having poor sleep quality were predictors of mental distress. Findings point to the need to devise evidence-driven interventions and strategies to prevent and reduce the problem of mental distress among students.