bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Is the health system ready?” A qualitative exploration of stakeholders’ opinions about the feasibility of preconception care services in the Nigerian health system
Authors: Ojifinni Oludoyinmola O. , Ibisomi Latifat 
Published: June 2022

Abstract
Background
Preconception care (PCC) services aim to improve reproductive health outcomes through the provision of biomedical, behavioural and social health interventions to women and couples before conception occurs. Countries that have deployed PCC services have policies that guide the services provided. In Nigeria, PCC is poorly developed and is often provided in an opportunistic manner with no guidelines in place to direct the provision. This study explored the opinions of policymakers and health workers about the feasibility of deploying PCC services in the country.

Methods
This study was a qualitative exploration of opinions about PCC service deployment within the Nigerian health system in which 39 in-depth interviews were conducted with policymakers at the federal and state tiers of government as well as health workers at the tertiary, secondary and primary levels of health care. The transcripts were analysed thematically using a hybrid of deductive and inductive coding on MAXQDA 2018 qualitative data analysis software.

Results
Four main themes emerged from the data—issues around policy for PCC, service integration and collaboration, health system readiness and challenges to PCC service deployment. While noting that the country has no PCC policy, participants identified existing policies into which PCC can be integrated. The participants also described the importance of policy to PCC provision and provided information on existing collaborations that can help the policy development and implementation process. Although many of the participants believed the health system is prepared for PCC deployment, they identified challenges related to policy formulation and implementation, including financial challenges that could hinder the process.

Conclusion
Deployment of PCC services in the Nigerian health system is achievable as there are existing health-related policies into which the guidelines can be integrated. However, there is a need to consider the possible implementation challenges and address them as part of the planning process.
Association of pre-pregnancy body mass index and gestational weight gain with neonatal anogenital distance in a Chinese birth cohort
Authors: Wang Zhiyang , Niu Jinbo , Ji Honglei , Miao Maohua , Yang Limei , Chen Xia , Li Xiufeng , Song Xiuxia , Chen Aimin , Liang Hong , Yuan Wei 
Published: June 2022

Abstract
Background
This study aimed to investigate the associations of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with anogenital distance (AGD) among newborns.

Methods
The study included 556 mother-newborn pairs from the Jiashan birth cohort. AGD was measured as AGDAP (from the center of the anus to the anterior base of the penis, where the penile tissue meets the pubic bone) and AGDAS (from the center of the anus to the posterior base of the scrotum, where the skin changes from rugate to smooth) in males and AGDAC (from the center of the anus to the clitoris) and AGDAF (from the center of the anus to the posterior convergence of the fourchette) in females. Multiple linear regression models were used to estimate the associations of pre-pregnancy BMI and GWG, with AGD.

Results
After adjusting for pre-pregnancy BMI and other potential confounders, male newborns whose mothers had excessive GWG had shorter AGDAP than those whose mothers had normal GWG. Male newborns whose mothers had normal pre-pregnancy BMI and inadequate/excessive GWG had shorter AGDAP than the reference group where mothers had normal pre-pregnancy BMI and GWG in stratified analyses.

Conclusion
Gestational weight gain during pregnancy was associated with AGD in newborns in this birth cohort.
Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus
Authors: Barbuskaite Dagne , Oernbo Eva K. , Wardman Jonathan H. , Toft-Bertelsen Trine L. , Conti Eller , Andreassen Søren N. , Gerkau Niklas J. , Rose Christine R. , MacAulay Nanna 
Published: June 2022

Abstract
Background
Elevated intracranial pressure (ICP) is observed in many neurological pathologies, e.g. hydrocephalus and stroke. This condition is routinely relieved with neurosurgical approaches, since effective and targeted pharmacological tools are still lacking. The carbonic anhydrase inhibitor, acetazolamide (AZE), may be employed to treat elevated ICP. However, its effectiveness is questioned, its location of action unresolved, and its tolerability low. Here, we determined the efficacy and mode of action of AZE in the rat .

Methods
We employed in vivo approaches including ICP and cerebrospinal fluid secretion measurements in anaesthetized rats and telemetric monitoring of ICP and blood pressure in awake rats in combination with ex vivo choroidal radioisotope flux assays and transcriptomic analysis.

Results
AZE effectively reduced the ICP, irrespective of the mode of drug administration and level of anaesthesia. The effect appeared to occur via a direct action on the choroid plexus and an associated decrease in cerebrospinal fluid secretion, and not indirectly via the systemic action of AZE on renal and vascular processes. Upon a single administration, the reduced ICP endured for approximately 10 h post-AZE delivery with no long-term changes of brain water content or choroidal transporter expression. However, a persistent reduction of ICP was secured with repeated AZE administrations throughout the day.

Conclusions
AZE lowers ICP directly via its ability to reduce the choroid plexus CSF secretion, irrespective of mode of drug administration.
Primary cold atmospheric plasma combined with low dose cisplatin as a possible adjuvant combination therapy for HNSCC cells—an in-vitro study
Authors: Brunner Teresa F. , Probst Florian A. , Troeltzsch Matthias , Schwenk-Zieger Sabina , Zimmermann Julia L. , Morfill Gregor , Becker Sven , Harréus Ulrich , Welz Christian 
Published: June 2022

Abstract
Background
The aim of the present study was to examine the cytostatic effects of cold atmospheric plasma (CAP) on different head and neck squamous carcinoma (HNSCC) cell lines either in isolation or in combination with low dose cisplatin. The effect of CAP treatment was investigated by using three different HNSCC cell lines (chemo-resistant Cal 27, chemo-sensitive FaDu and OSC 19).

Materials and method
Cell lines were exposed to CAP treatment for 30, 60, 90, 120 and 180 s (s). Cisplatin was added concurrently (cc) or 24 h after CAP application (cs). Cell viability, DNA damage and apoptosis was evaluated by dye exclusion, MTT, alkaline microgel electrophoresis assay and Annexin V-Fit-C/PI respectively.

Results
In all cell lines, 120 s of CAP exposure resulted in a significant reduction of cell viability. DNA damage significantly increased after 60 s. Combined treatment of cells with CAP and low dose cisplatin showed additive effects. A possible sensitivity to cisplatin could be restored in Cal 27 cells by CAP application.

Conclusion
CAP shows strong cytostatic effects in HNSCC cell lines that can be increased by concurrent cisplatin treatment, suggesting that CAP may enhance the therapeutic efficacy of low dose cisplatin.
Bookend: precise transcript reconstruction with end-guided assembly
Authors: Schon Michael A. , Lutzmayer Stefan , Hofmann Falko , Nodine Michael D. 
Published: June 2022

AbstractWe developed Bookend, a package for transcript assembly that incorporates data from different RNA-seq techniques, with a focus on identifying and utilizing RNA 5′ and 3′ ends. We demonstrate that correct identification of transcript start and end sites is essential for precise full-length transcript assembly. Utilization of end-labeled reads present in full-length single-cell RNA-seq datasets dramatically improves the precision of transcript assembly in single cells. Finally, we show that hybrid assembly across short-read, long-read, and end-capture RNA-seq datasets from Arabidopsis thaliana, as well as meta-assembly of RNA-seq from single mouse embryonic stem cells, can produce reference-quality end-to-end transcript annotations.
Deletion of Fmr1 in parvalbumin-expressing neurons results in dysregulated translation and selective behavioral deficits associated with fragile X syndrome
Authors: Kalinowska Magdalena , van der Lei Mathijs B. , Kitiashvili Michael , Mamcarz Maggie , Oliveira Mauricio M. , Longo Francesco , Klann Eric 
Published: June 2022

Abstract
Background
Fragile X syndrome (FXS), the most common genetic cause of autism spectrum disorder and intellectual disability, is caused by the lack of fragile X mental retardation protein (FMRP) expression. FMRP is an mRNA binding protein with functions in mRNA transport, localization, and translational control. In Fmr1 knockout mice, dysregulated translation has been linked to pathophysiology, including abnormal synaptic function and dendritic morphology, and autistic-like behavioral phenotypes. The role of FMRP in morphology and function of excitatory neurons has been well studied in mice lacking Fmr1, but the impact of Fmr1 deletion on inhibitory neurons remains less characterized. Moreover, the contribution of FMRP in different cell types to FXS pathophysiology is not well defined. We sought to characterize whether FMRP loss in parvalbumin or somatostatin-expressing neurons results in FXS-like deficits in mice.

Methods
We used Cre-lox recombinase technology to generate two lines of conditional knockout mice lacking FMRP in either parvalbumin or somatostatin-expressing cells and carried out a battery of behavioral tests to assess motor function, anxiety, repetitive, stereotypic, social behaviors, and learning and memory. In addition, we used fluorescent non-canonical amino acid tagging along with immunostaining to determine whether de novo protein synthesis is dysregulated in parvalbumin or somatostatin-expressing neurons.

Results
De novo protein synthesis was elevated in hippocampal parvalbumin and somatostatin-expressing inhibitory neurons in Fmr1 knockout mice. Cell type-specific deletion of Fmr1 in parvalbumin-expressing neurons resulted in anxiety-like behavior, impaired social behavior, and dysregulated de novo protein synthesis. In contrast, deletion of Fmr1 in somatostatin-expressing neurons did not result in behavioral abnormalities and did not significantly impact de novo protein synthesis. This is the first report of how loss of FMRP in two specific subtypes of inhibitory neurons is associated with distinct FXS-like abnormalities.

Limitations
The mouse models we generated are limited by whole body knockout of FMRP in parvalbumin or somatostatin-expressing cells and further studies are needed to establish a causal relationship between cellular deficits and FXS-like behaviors.

Conclusions
Our findings indicate a cell type-specific role for FMRP in parvalbumin-expressing neurons in regulating distinct behavioral features associated with FXS.
Outer trench slope extension to frontal wedge compression in a subducting plate
Authors: Chang Emmy T. , Mozziconacci Laetitia 
Published: June 2022

AbstractThe occurrence of faulting in subducting plates is a major process that changes the mechanical properties of the subducting lithosphere and carries surface materials into mantle wedges. Two ocean-bottom seismometer networks deployed on the frontal accretionary wedge of the northern Manila trench in 2005 and on the outer slope of the trench in 2006 were used to detect earthquakes in the subducting plate. All available P and S manually picked phases and the waveforms of 16 short-period, three-component stations were used. Relocation was performed using the double-difference method with differential times derived from the phase-picked data. Two intraplate earthquake sequences of small-to-moderate magnitudes in the northern Manila subduction system were investigated in this study. The results revealed distinct fault planes, but a contrasting seismogeny over the northern Manila Trench. The seismicity in the frontal wedge (as measured in 2005) was mainly contributed by a fluid overpressure sequence, whereas that in the incoming plate (as measured in 2006) was contributed by the aftershocks of an extensional faulting sequence. The obtained seismic velocity models and Vp/Vs ratios revealed that the overpressure was likely caused by high pore-fluid pressure within the shallow subduction zone. By using the near-field waveform inversion algorithm, we determined focal mechanism solutions for a few relatively large earthquakes. Through the use of data obtained from global seismic observations, we determined that stress transfer may be responsible for the seismic activity in the study area during the period of 2005–2006. In late 2005, the plate interface in the frontal wedge area was unlocked by the overpressure effect due to a thrusting-dominant sequence. This event changed the stress regime across the Manila Trench and triggered a normal fault extension at the outer trench slope in mid-2006. However, in the present study, a hybrid focal mechanism solution indicating reverse and strike–slip mechanisms was implemented, and it revealed that the plate interface locked again in late 2006.
Graphical Abstract
Association of ABO blood groups and ART outcomes among subfertile South Asian women: a retrospective cohort study
Authors: Jayakumar Nithya Panapakkam , Reka Karuppusami , Parimala Chinta , Kunjummen Aleyamma Thayparmbil , Kamath Mohan Shashikant 
Published: June 2022

Abstract
Background
Blood groups are expressed on the surface of the red cells, and their association with the ovarian reserve and pregnancy outcomes has been an area of interest. The aim of the current study is to study the association of blood groups with live birth rates among South Asian women undergoing assisted reproductive technology treatment. It is a retrospective cohort analysis of women undergoing assisted reproductive technology (ART) at Christian Medical College and Hospital, India, between January 2007 and June 2017. All women ≤ 40 years undergoing the first ART cycle with fresh embryo transfer were included and stratified into four groups (A, B, AB, and O) based on the blood group type. The ART outcomes were analyzed among the groups.

Results
A total of 2524 women underwent fresh embryo transfer cycles during the study period, among whom 2079 women were analyzed. There was no statistically significant difference in the live birth rates for women with blood group B (odds ratio, OR 0.96, confidence interval, CI, 95% 0.74–1.24), blood group AB (OR 0.89, 95% CI 0.58–1.35), and blood group O (OR 0.87, 95% CI 0.68–1.12) with blood group A as the reference. After adjusting for important confounders, there was no statistically significant difference in the live birth rates for women with blood group B, AB, and O in comparison with blood group A.

Conclusion
The current study showed no association of blood groups with the ART treatment outcomes in South Asian women.
Camrelizumab in combination with concurrent chemoradiotherapy as first-line treatment for nonoperative head and neck cancer: A comparative study.
Authors: Liu Feng , Huang Wenxiao , Wang Hui , Jiang Cuihong , Zhang Hailin , Wu Xiangwei , Tan Haolei , Li Jinyun , Tan Pingqing , He Lili , Xiao Shuai 
Published: June 2022

6063 Background: We hypothesized that concurrent chemoradiotherapy (CCRT) plus concurrent and adjuvant camrelizumab as first-line treatmentwas associated with improved survival compared with concurrent chemoradiotherapy alone for nonoperative locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The purpose of this comparative study was to compare the efficacy and toxicity of CCRT plus concurrent and adjuvant camrelizumab versus CCRT alone in nonoperative locoregionally advanced HNSCC. Methods: One hundred and eighty patients with nonoperative locoregionally advanced HNSCC (cancer of the oral cavity, oropharyngeal cancer, hypopharyngeal cancer and laryngeal cancer) received either CCRT plus concurrent and adjuvant camrelizumab (camrelizumab + CCRT group, n = 90) or CCRT alone (CCRT alone group, n = 90). Patients in both groups received curative cisplatin-based concurrent chemoradiotherapy. The radiation dose was 70 Gy (2.0 Gy/fraction). In camrelizumab + CCRT group, concurrent camrelizumab (200mg/day on days 1, 22, 43) was added to CCRT, followed by adjuvant camrelizumab (200mg, every 3 weeks for 6 months or until disease progression, unacceptable adverse events or withdrawal of consent). Results: Compared with CCRT alone, the addition of concurrent and adjuvant camrelizumab significantly improved complete response (CR) rates (92.2% vs. 80.0%; P = 0.018), 3-year disease free survival (DFS, 72.2% vs. 56.7%; P = 0.029), locoregional recurrence-free survival (LRRFS, 76.7% vs. 61.1%; P = 0.024), and overall survival (OS, 78.9% vs. 63.3%; P = 0.033). Reactive cutaneous capillary endothelial proliferation was higher in the camrelizumab + CCRT group (6.7% vs. 0.0%; P = 0.013). No statistically significant differences in other acute (mucositis, leukopenia, thrombocytopenia, anemia, etc.) and late toxic effects (mucosal necrosis, trismus, cranial nerve palsy, etc.) were observed between the two groups. The addition of camrelizumab (CCRT plus camrelizumab vs. CCRT alone) was a significant independent prognostic factor for 3-year DFS, LRRFS and OS (P = 0.038, P = 0.032, and P = 0.048, respectively). Conclusions: Concurrent chemoradiotherapy plus concurrent and adjuvant camrelizumab as first-line treatment is associated with a considerable survival benefit, with acceptable adverse events, as compared with concurrent chemoradiotherapy alone, among patients with nonoperative locoregionally advanced head and neck squamous cell carcinoma. Our ongoing prospective clinical trial (registered with chictr.org.cn, number ChiCTR2200056298) will further investigate the efficacy of camrelizumab in combination with chemoradiotherapy for HNSCC.
Transoral robotic surgery (TORS)-guided radiotherapy (RT) volume de-intensification in p16-positive unknown primary squamous cell carcinoma (SCC) of the neck: A phase 2 trial (FIND).
Authors: de Almeida John R , Goldstein David Paul , Martino Rosemary , Su Jie , Hosni Ali , Bratman Scott Victor , Chepeha Douglas Brian , Waldron John , Weinreb Ilan , Perez-Ordonez Bayardo , Yu Eugene , Metser Ur , Hansen Aaron Richard , Xu Wei , Kim John 
Published: June 2022

6067 Background: TORS has improved the likelihood of identifying an oropharyngeal cancer for patients presenting with unknown primary. We evaluate the oncologic and functional outcomes after reduction of RT volumes based on TORS findings. Methods: Patients with p16-positive, neck SCC (cN1-N3) with no primary on examination and CT/MRI were included between 08/2017 and 12/2019. All patients underwent PET-CT, surgical evaluation with either therapeutic intent including neck dissection for cN1 without extranodal extension (Group 1, n=9) or diagnostic intent (Group 2, n=13). Patients underwent excision of palatine tonsil (PT) followed by lingual tonsil (LT), if the PT was negative, or excision of PET-CT avid regions. Pharyngeal-sparing radiotherapy (PSRT) was given when no primary was found (pT0) and for primaries completely excised (margins >= 3mm). Unilateral neck radiotherapy (UNRT) was given for lateralized (>1 cm from midline) primaries or pT0 with unilateral disease. The primary outcome was 2-year out-of-treated volume failures (OTVF). Swallowing-related quality of life (SR-QOL) was measured using MD Anderson Dysphagia Inventory (MDADI) composite score. A sample size of 22 was required assuming OTVF cannot exceed 15% (vs. 1% historical), power of 0.8, alpha of 0.05 (one-sided), and loss to follow-up of 10%. Results: All 22 patients [median age 60 (46-68); 86% male; 86% N1, 9% N2, 5% N3] underwent surgical evaluation. PET-CT showed suspicious findings in 12 (55%) [sensitivity = 0.44, specificity = 0.29]. Excision of PT and LT were performed in 14 (64%) and 14 (64%) patients respectively; and 8 (36%) had previous PT. Oropharyngeal primaries were found in 17 patients (77%) [14 (64%) single primary, 3 (13%) two primaries]. RT volume de-intensification was achieved in 11 patients (50%) who had PSRT and 10 (45%) who had UNRT. In Group 1, adjuvant RT was given to 6 (67%) and CRT to 1 (11%). In group 2, 8 (62%) had RT and 5 (38%) had CRT. There were no OTVF, local, or regional failures [median follow-up 29 months]. Two-year OS, DFS, and LRC were 100%, 95%, and 100%. SR-QOL showed good recovery (Table). Grade III/IV surgical as well as acute and late toxicities occurred in 2 (9%), 5 (23%), and 1 (5%) respectively. Conclusions: TORS evaluation for p16-positive unknown primary SCC allowed RT volume de-intensification with excellent disease control and quality of life. Future randomized trials can compare transoral surgery versus existing diagnostic approaches. MDADI composite scores. Clinical trial information: NCT03281499. [Table: see text]
Cabozantinib (C) versus placebo (P) in patients (pts) with radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) who have progressed after prior VEGFR-targeted therapy: Outcomes in prespecified subgroups based on prior VEGFR-targeted therapy.
Authors: Hernando Jorge , Capdevila Jaume , Robinson Bruce , Sherman Steven I. , Jarząb Barbara , Lin Chia-Chi , Vaisman Fernanda , Hoff Ana , Hitre Erika , Bowles Daniel W. , Sen Suvajit , Oliver Jennifer Wright , Keam Bhumsuk , Brose Marcia S. 
Published: June 2022

6083 Background: Based on the results of the phase 3 COSMIC-311 trial, the multikinase inhibitor C was recently approved by the FDA for the treatment of RAIR DTC pts who progress after prior VEGFR-targeted therapies, such as lenvatinib (L) or sorafenib (S), and for whom there was no standard of care (Brose et al. Lancet Oncol. 2021). In an extended follow-up of the intent-to-treat (ITT) population, C-treated pts achieved a median (m) progression-free survival (PFS) of 11 months (mo) vs 1.9 mo with P (HR 0.22, 96% CI 0.15–0.32, P <.0001); here we present outcomes for prespecified subgroups who received prior L, S, or both. Methods: Pts were randomized 2:1 to C (60 mg QD) or P. P pts could cross over to open-label C upon disease progression per confirmation by blinded independent radiology committee (BIRC). The primary endpoints were PFS (ITT) and objective response rate (first 100 randomized pts), per RECIST v1.1 by BIRC. Pts must have received L or S and progressed during or after 1–2 prior VEGFR inhibitors. Results: After a median follow-up of 10.1 mo, 258 pts (170 C, 88 P) had been randomized (data cutoff 8 Feb 2021); 96 (̃37%) had received prior S (no L), 102 (̃40%) prior L (no S), and 60 (̃23%) prior S and L. Median PFS was 16.6 for C vs 3.2 mo for P in prior S (no L) (HR 0.13, 95% CI 0.06–0.26); 5.8 vs 1.9 mo in prior L (no S) (HR 0.28, 95% CI 0.16–0.48), and 7.6 vs 1.9 mo in prior S and L (HR 0.27, 95% CI 0.13–0.54). In the C arm, 21% of pts in prior S (no L), 3% in prior L (no S), and 8% in S and L subgroups had confirmed partial response, and 1 pt had a confirmed complete response in prior L (no S); there were no responses with P. Stable disease as best response was 67% for C vs 45% for P in prior S (no L), 68% vs 32% in prior L (no S), and 74% vs 38% in prior S and L. Median duration of C-exposure was 7.0 mo in prior S (no L), 5.6 mo in prior L (no S) and 5.9 mo in prior S and L. Grade 3/4 treatment-emergent adverse events (TEAE) occurred in 63% pts in prior S (no L), 57% in prior L (no S), and 69% in prior S and L. Discontinuations of C due to TEAE occurred in 16% of pts in prior S (no L), 13% in prior L (no S), and 23% in prior S and L. There were no treatment-related deaths. Conclusions: In the extended follow-up, C maintained its superior PFS vs P irrespective of prior L and/or S. AEs in each subgroup were consistent with that of the overall population. This is also the first phase 3 study demonstrating a clinical benefit with C after prior L in RAIR DTC pts. Clinical trial information: NCT03690388.