bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three weekly versus weekly concurrent cisplatin: safety propensity score analysis on 166 head and neck cancer patients
Authors: Buglione Michela , Alterio Daniela , Maddalo Marta , Greco Diana , Gerardi Marianna Alessandra , Tomasini Davide , Pegurri Ludovica , Augugliaro Matteo , Marvaso Giulia , Turturici Irene , Guerini Andrea , Ansarin Mohssen , Spiazzi Luigi , Costa Loredana , Cossu Rocca Maria , Magrini Stefano Maria , Jereczek-Fossa Barbara Alicja 
Published: December 2021

Abstract
Background
Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m2/q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m2/q1.

Methods
Patients were treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules.

Results
Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule.

Conclusions
3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients.
Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway
Authors: Xue Lianguo , Jia Tao , Zhu Yuanxin , Zhao Lidong , Mao Jianping 
Published: December 2021

AbstractBackgroundMultiple myeloma (MM) is one of the most frequently diagnosed hematological malignancy. Dysregulation of circular RNAs (circRNAs) has important impacts on MM process. Herein, this work aimed to investigate the role and mechanism of circ_0058058 in MM progression.MethodsLevels of genes and proteins were detected by real-time reverse transcription PCR (RT-qPCR) and Western blot. CCK-8 assay, colony formation assay, EdU assay, flow cytometry, tube formation assay, transwell assay and Western blot were utilized to detect the proliferation, apoptosis, angiogenesis and metastasis of MM cells. The target relationship between miR-338-3p and circ_0058058 or ATG14 (autophagy related 14) was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In vivo experiments were performed using Xenograft assay.ResultsCirc_0058058 was up-regulated in MM bone marrow aspirates and cells, knockdown of circ_0058058 reduced MM cell proliferation, angiogenesis and metastasis, but induced apoptosis in vitro. In a MM xenograft mouse model, circ_0058058 silencing reduced MM tumor growth and cell proliferation. Mechanistically, circ_0058058 acted as a sponge for miR-338-3p to up-regulate ATG14 expression, which was validated to be a target of miR-338-3p. Rescue assay showed that miR-338-3p inhibition reversed the antitumor effects of circ_0058058 knockdown on MM cell. Moreover, forced expression of miR-338-3p suppressed MM cell malignant phenotype, which was abolished by ATG14 up-regulation.ConclusionCirc_0058058 functions as a sponge for miR-338-3p to elevate ATG14 expression to promote MM cell proliferation, metastasis and angiogenesis, affording a potential therapeutic target for MM prevention.
Pathways to mental health care in Nepal: a 14-center nationwide study
Authors: Gupta Anoop Krishna , Joshi Sulochana , Kafle Bikram , Thapa Ranjan , Chapagai Manisha , Nepal Suraj , Niraula Abhash , Paudyal Sreya , Sapkota Prabhat , Poudel Reet , Gurung Bina Sing , Pokhrel Prabhakar , Jha Robin , Pandit Sanjib , Thapaliya Suresh , Shrestha Shuva , Volpe Umberto , Sartorius Norman 
Published: December 2021

Abstract
Background
Pathways to care studies are feasible and tested means of finding the actual routes taken by patients before reaching proper care. In view of the predominance of nonprofessional service providers and the lack of previous large studies on pathways in Nepal, this multicenter study is needed. The aim of the study was to trace the various pathways and carers involved in mental health care; assess clinical variables such as the duration of untreated illness, clinical presentation and treatment; and compare geographically and culturally diverse landscapes.

Methods
This was a cross-sectional, convenience sampling study performed at 14 centers where new cases were being taken. The World Health Organization Study of the Pathways-to-Care Schedule was applied. The Nepali version of the encounter form was used. The data were collected between 17 September and 16 October 2020 and were analyzed using the Statistical Package for the Social Sciences (SPSS). Additionally, perspectives from local investigators were collected and discussed.

Results
Most of the first carers were native/religious faith healers (28.2%), followed by psychiatrists (26%). The median duration for the first psychiatric consultation was 3 weeks. The duration of untreated illness was 30.72 ± 80.34 (median: 4) weeks, and the time taken for this journey was 94.99 ± 274.58 (median: 30) min. The longest delay from the onset of illness to psychiatric care was for epilepsy {90.0 ± 199.0 (median: 25.5)} weeks, followed by neurotic illness {22.89 ± 73.45 (median: 2)} and psychotic illness {10.54 ± 18.28 (median: 2)} weeks. Overall, most patients with severe mental illnesses (SMIs) had their first contact with faithhealers (49%), then met with medical doctors (13%) or psychiatrists (28%). Marked differences in clinical presentation surfaced when hilly centers were compared with the Terai belt.

Conclusions
Faith healers, general practitioners and hospital doctors are major carers, and the means of educating them for proper referral can be considered. The investigators see several hindrances and opportunities in the studied pathways. The employment of more mental health professionals and better mental health advocacy, public awareness programs and school education are suggested strategies to improve proper mental health care.
OPHTHALMIA NEONATORUM in Italy: it is time for change
Authors: Auriti Cinzia , Mondì Vito , Aversa Salvatore , Merazzi Daniele , Lozzi Simona , Petroni Sergio , Baldascino Antonio , Massenzi Luca , Bellù Roberto , Martinelli Stefano , Mosca Fabio 
Published: December 2021

AbstractOphthalmia neonatorum (ON) refers to any conjunctivitis occurring in the first 28 days of life. In the past Neisseria gonorrhoeae was the most common cause of ON. It decreased with the introduction of prophylaxis at birth with the instillation of silver nitrate 2% (the Credè’s method of prophylaxis). Today, the term ON is used to define any other bacterial infection, in particular due to Chlamydia Trachomatis. Currently, the WHO reccomends topical ocular prophylaxis for prevention of gonococcal and chlamydial conjunctivitis for all neonates. On the contrary, several European countries no longer require universal prophylaxis, opting for screening and treatment of pregnant women at high risk of infection. And what about Italy? Have a look on Italian history of prophylaxis, starting by the first decree issued in 1940, signed by Benito Mussolini. In the following decades the law has undergone many changes. At the moment, legislation is unclear, therefore careful consideration is required in order to draft the correct appoach.
HIV-1LAI Nef blocks the development of hematopoietic stem/progenitor cells into myeloid-erythroid lineage cells
Authors: Zou Wei , Xing Juanjuan , Zou Shijie , Jiang Mei , Chen Xinping , Chen Qi , Liu Daozheng , Zhang Xiangcheng , Fu Xin 
Published: December 2021

Abstract
Background
A variety of hematopoietic abnormalities are commonly seen in human immunodeficiency virus-1 (HIV-1) infected individuals despite antiviral therapy, but the underlying mechanism remains elusive. Nef plays an important role in HIV-1 induced T cell loss and disease progression, but it is not known whether Nef participates in other hematopoietic abnormalities associated with infection.

Results
In the current study we investigated the influence of HIV-1LAI Nef (LAI Nef) on the development of hematopoietic stem/progenitor cells (HSPCs) into myeloid-erythroid lineage cells, and found that nef expression in HSPCs blocked their differentiation both in vitro and in humanized mice reconstituted with nef-expressing HSPCs.

Conclusions
Our novel findings demonstrate LAI Nef compromised the development of myeloid-erythroid lineage cells, and therapeutics targeting Nef would be promising in correcting HIV-1 associated hematopoietic abnormalities.
Augmenting an online self-directed intervention for gambling disorder with a single motivational interview: study protocol for a randomized controlled trial
Authors: Brazeau Brad W. , Hodgins David C. , Cunningham John A. , Bennett Kylie , Bennett Anthony 
Published: December 2021

Abstract
Background
Despite the success of gold standard cognitive-behavioral therapy for problem and disordered gambling, the majority of individuals with gambling problems do not seek or receive professional treatment. Thus, the development of less intrusive self-directed interventions has been encouraged. Bibliotherapy for problem gambling has shown promise, both alone and in combination with motivational interviews, but there is still a lack of online self-directed intervention research. The current randomized controlled trial proposes to assess the additive benefit of a single digital motivational interview delivered in conjunction with an online self-directed treatment program for problem gambling and gambling disorder.

Methods
A two-arm randomized controlled trial will be conducted, wherein eligible participants (N=270) will be recruited across Canada via internet advertisements posted to several platforms. All participants will receive access to an online self-directed gambling intervention program. Participants will be randomly assigned to either complete the online program alone or receive a digital motivational interview, conducted through an online audioconferencing platform (i.e., Microsoft Teams) to supplement the online program. The primary outcomes of gambling severity, frequency, and expenditures will be tracked along with secondary outcomes (i.e., depression, anxiety, general distress, alcohol use, and online program user data) over a 24-month period. It is expected that participants in both groups will experience a reduction in symptoms across the board, but more substantial improvements will be observed in the group that receives a supplemental motivational interview.

Discussion
The results of this trial will expand upon prior gambling intervention research by informing best practices for the provision of online self-help for problem gambling.

Trial registration
ISRCTN ISRCTN13009468. Registered on 7 July 2020.
The ecdysteroid receptor regulates salivary gland degeneration through apoptosis in Rhipicephalus haemaphysaloides
Authors: Lu Xiaojuan , Zhang Zhipeng , Yuan Dongqi , Zhou Yongzhi , Cao Jie , Zhang Houshuang , da Silva Vaz Itabajara , Zhou Jinlin 
Published: December 2021

Abstract
Background
It is well established that ecdysteroid hormones play an important role in arthropod development and reproduction, mediated by ecdysteroid receptors. Ticks are obligate hematophagous arthropods and vectors of pathogens. The salivary gland plays an essential role in tick growth and reproduction and in the transmission of pathogens to vertebrate hosts. During tick development, the salivary gland undergoes degeneration triggered by ecdysteroid hormones and activated by apoptosis. However, it is unknown how the ecdysteroid receptor and apoptosis regulate salivary gland degeneration. Here, we report the functional ecdysteroid receptor (a heterodimer of the ecdysone receptor [EcR] and ultraspiracle [USP]) isolated from the salivary gland of the tick Rhipicephalus haemaphysaloides and explore the molecular mechanism of ecdysteroid receptor regulation of salivary gland degeneration.

Methods
The full length of RhEcR and RhUSP open reading frames (ORFs) was obtained from the transcriptome. The RhEcR and RhUSP proteins were expressed in a bacterial heterologous system, Escherichia coli. Polyclonal antibodies were produced against synthetic peptides and were able to recognize recombinant and native proteins. Quantitative real-time PCR and western blot were used to detect the distribution of RhEcR, RhUSP, and RhCaspases in the R. haemaphysaloides organs. A proteomics approach was used to analyze the expression profiles of the ecdysteroid receptors, RhCaspases, and other proteins. To analyze the function of the ecdysteroid receptor, RNA interference (RNAi) was used to silence the genes in adult female ticks. Finally, the interaction of RhEcR and RhUSP was identified by heterologous co-expression assays in HEK293T cells.

Results
We identified the functional ecdysone receptor (RhEcR/RhUSP) of 20-hydroxyecdysone from the salivary gland of the tick R. haemaphysaloides. The RhEcR and RhUSP genes have three and two isoforms, respectively, and belong to a nuclear receptor family but with variable N-terminal A/B domains. The RhEcR gene silencing inhibited blood-feeding, blocked engorgement, and restrained salivary gland degeneration, showing the biological role of the RhEcR gene in ticks. In the ecdysteroid signaling pathway, RhEcR silencing inhibited salivary gland degeneration by suppressing caspase-dependent apoptosis. The heterologous expression in mammalian HEK293T cells showed that RhEcR1 interacts with RhUSP1 and induces caspase-dependent apoptosis.

Conclusions
These data show that RhEcR has an essential role in tick physiology and represents a putative target for the control of ticks and tick-borne diseases.

Graphical Abstract
In vitro characterization of Haemonchus contortus trehalose-6-phosphate phosphatase and its immunomodulatory effects on peripheral blood mononuclear cells (PBMCs)
Authors: Wen ZhaoHai , Xie XinRan , Aleem Muhammad Tahir , Aimulajiang Kalibixiati , Chen Cheng , Liang Meng , Song XiaoKai , Xu LiXin , Li XiangRui , Yan RuoFeng 
Published: December 2021

Abstract
Background
Trehalose-6-phosphate phosphatase (TPP6) is a key enzyme in the trehalose biosynthesis pathway. The accumulation of TPP6 inside the body is harmful to the pathogen, but almost nothing is currently known about the function of TPP6 from Haemonchus contortus (CRE-GOB-1).

Methods
The H. contortus CRE-GOB-1 (HcGOB) gene was cloned and recombinant protein of GOB (rHcGOB) was expressed; transcription of the HcGOB gene at different developmental stages of H. contortus was then studied. The spatial expression pattern of the HcGOB gene in adult female and male worms was determined by both quantitative real-time PCR (qPCR) and immunofluorescence. The binding of the rHcGOB protein to goat PBMCs was assessed by immunofluorescence assay. The immunomodulatory impacts of rHcGOB on cell proliferation, nitric oxide generation and cytokine secretion were assessed by co-culture of rHcGOB protein with goat PBMCs.

Results
The HcGOB protein was transcribed in eggs, infective third-stage larvae (iL3s) and adults of H. contortus, with the highest transcript levels found in the egg stage. The transcript levels were significantly elevated in iL3s after manual desheathing. HcGOB was widely distributed in adult worms where it was mainly localized in the gut and gonads. rHcGOB was observed to bind to PBMCs and also to be recognized by sera collected from a goat infected with H. contortus. rHcGOB significantly activated the interleukin-10/transforming growth factor β/signal transducer and activator of transcription 3 (IL-10/TGF-β/STAT3) pathway in PBMCs while suppressing the transcription and expression of IL-4 and IL-17.

Conclusions
These results suggest that the HcGOB gene plays an important role in the development, parasitism and reproduction of H. contortus. The rHcGOB protein affected the immunomodulatory function of PBMCs in the in vitro study, suggesting that this protein would be a promising vaccine target.

Graphical Abstract
Can adults with cerebral palsy perform and benefit from ballistic strength training to improve walking outcomes? A mixed methods feasibility study
Authors: Gjesdal Beate Eltarvåg , Mæland Silje , Williams Gavin , Aaslund Mona Kristin , Rygh Cecilie Brekke , Cumming Kristoffer Toldnes 
Published: December 2021

Abstract
Background
Power bursts of hips and ankle plantar flexors are prerequisites to walking propulsion. However, these power bursts are reduced during gait for persons with cerebral palsy (CP) and mainly in the ankle plantar flexors. Hence, task specific training, such as ballistic strength training, is suggested to increase muscle power in walking but not investigated in adults with CP. Therefore, the aim was to investigate if adults with CP could perform and benefit from ballistic strength training to improve walking, evaluated through physical measures and self-reported measures and interviews.

Methods
In this mixed methods feasibility study, eight ambulatory adults (aged 24–56) with spastic CP conducted ballistic strength training on a glideboard targeting the ankle plantarflexors two times a week for eight weeks. The feasibility of the training was assessed through objectives described by Orsmond and Cohn. Before and after the intervention, physical measures (6-Minute Walk Test and the eight-item High-level Mobility Assessment Tool) and self-reported measures (Patient Global Impression of Change, Numeric Pain Rating Scale, Fatigue Impact and Severity Self-Assessment, and Walk-12) were collected. After the intervention, semi-structured interviews explored experiences of this training.

Results
The participants experienced training the ankle plantar flexor as relevant but reported it took about four weeks to coordinate the exercises successfully. Although we observed no changes in the physical performance measures, most participants reported improvements; some felt steadier when standing, walking, and hopping.

Conclusion
This study demonstrated that ballistic strength training was feasible and suitable in adults with CP. However, guidance and a long (4 weeks) familiarization time were reported necessary to master the exercises. Most participants reported self-experienced improvements, although no physical performance measures improved. Thus, prolonged intervention may be required for perceived physical improvements to emerge. Also, other outcome measures sensitive to power output remains to be investigated.
Lessons learned during implementation of MR-guided High-Intensity Focused Ultrasound treatment of uterine fibroids
Authors: Anneveldt K. J. , Verpalen I. M. , Nijholt I. M. , Dijkstra J. R. , van den Hoed R. D. , van’t Veer-ten Kate M. , de Boer E. , van Osch J. A. C. , Heijman E. , Naber H. R. , Ista E. , Franx A. , Veersema S. , Huirne J. A. F. , Schutte J. M. , Boomsma M. F. 
Published: December 2021

Abstract
Background
Although promising results have been reported for Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids, this treatment is not yet widely implemented in clinical practice. During the implementation of a new technology, lessons are learned and an institutional learning-curve often has to be completed. The primary aim of our prospective cohort study was to characterize our learning-curve based on our clinical outcomes. Secondary aims included identifying our lessons learned during implementation of MR-HIFU on a technical, patient selection, patient counseling, medical specialists and organizational level.

Results
Our first seventy patients showed significant symptom reduction and improvement of quality of life at 3, 6 and 12 months after MR-HIFU treatment compared to baseline. After the first 25 cases, a clear plateau phase was reached in terms of failed treatments. The median non-perfused volume percentage of these first 25 treatments was 44.6% (range: 0–99.7), compared to a median of 74.7% (range: 0–120.6) for the subsequent treatments.

Conclusions
Our findings describe the learning-curve during the implementation of MR-HIFU and include straightforward suggestions to shorten learning-curves for future users. Moreover, the lessons we learned on technique, patient selection, patient counseling, medical specialists and organization, together with the provided supplements, may be of benefit to other institutions aiming to implement MR-HIFU treatment of uterine fibroids.
Trial registration ISRCTN14634593. Registered January 12, 2021—Retrospectively registered, https://www.isrctn.com/ISRCTN14634593.
Risk of metastatic disease using [18F]PSMA-1007 PET/CT for primary prostate cancer staging
Authors: Chikatamarla Venkata Avinash , Okano Satomi , Jenvey Peter , Ansaldo Alexander , Roberts Matthew J. , Ramsay Stuart C. , Thomas Paul A. , Pattison David A. 
Published: December 2021

Abstract
Background
Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [68Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [18F]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [18F]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis.

Results
The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p < 0.001) and AJCC stage (p = 0.034). PSA > 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78–91%) and 60% (95% CI 50–68%) and a sensitivity of 36% (95% CI 25–49%) and 62% (95% CI 49–74%), respectively, for detection of metastatic disease.

Conclusion
Metastatic disease according to [18F]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [18F]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax.