bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving our model of cascade testing for hereditary cancer risk by leveraging patient peer support: a concept report
Authors: O’Neill Suzanne C. , Hamilton Jada G. , Conley Claire C. , Peshkin Beth N. , Sacca Rosalba , McDonnell Glynnis A. , Isaacs Claudine , Robson Mark E. , Tercyak Kenneth P. 
Published: September 2021

AbstractConsensus and evidence suggest that cascade testing is critical to achieve the promise of cancer genetic testing. However, barriers to cascade testing include effective family communication of genetic risk information and family members’ ability to cope with genetic risk. These barriers are further complicated by the developmental needs of unaffected family members during critical windows for family communication and adaptation. Peer support could address these barriers. We provide two illustrative examples of ongoingBRCA1/2-related clinical trials that apply a peer support model to improve family communication and functioning. Peer support can augment currently available genetic services to facilitate adjustment to and effective use of cancer genetic risk information. Importantly, this scalable approach can address the presence of cancer risk within families across multiple developmental stages. This applies a family-centered perspective that accommodates all potentially at-risk relatives. This peer support model can be further applied to emerging topics in clinical genetics to expand reach and impact.
Use of routinely collected health data in randomised clinical trials: comparison of trial-specific death data in the BOSS trial with NHS Digital data
Authors: Love Sharon B. , Kilanowski Anna , Yorke-Edwards Victoria , Old Oliver , Barr Hugh , Stokes Clive , Kendall Catherine , Sydes Matthew R. 
Published: September 2021

Abstract
Background
A promising approach to reduce the increasing costs of clinical trials is the use of routinely collected health data as participant data. However, the quality of this data could limit its usability as trial participant data.

Methods
The BOSS trial is a randomised controlled trial comparing regular endoscopies versus endoscopies at need in patients with Barrett’s oesophagus with primary endpoint death. Data on death and cancer collected every 2 years after randomisation (trial-specific data) were compared to data received annually (all patients on one date) from the routinely collected health data source National Health Service (NHS) Digital. We investigated completeness, agreement and timeliness and looked at the implications for the primary trial outcome. Completeness and agreement were assessed by evaluating the number of reported and missing cases and any disparities between reported dates. Timeliness was considered by graphing the year a death was first reported in the trial-specific data against that for NHS Digital data. Implications on the primary trial outcome, overall survival, of using one of the data sources alone were investigated using Kaplan-Meier graphs. To assess the utility of cause of death and cancer diagnoses, oesophageal cancer cases were compared.

Results
NHS Digital datasets included more deaths and often reported them sooner than the trial-specific data. The number reported as being from oesophageal cancer was similar in both datasets. Due to time lag in reporting and missing cases, the event rate appeared higher using the NHS Digital data.

Conclusion
NHS Digital death data is useful for calculating overall survival where trial-specific follow-up is only every 2 years from randomisation and the follow-up requires patient response. The cancer data was not a large enough sample to assess usability. We suggest that this assessment of registry data is done for more phase III RCTs and for more registry data to get a more complete picture of when RCHD would be useful in phase III RCT.

Trial registration
ISRCTN54190466 (BOSS) 1 Oct 2009.
Study protocol: a multi-center, double-blind, randomized, 6-month, placebo-controlled trial to investigate the effect of supplementing hormone therapy FET cycles with Gushen’antai pills on the outcomes of in vitro fertilization
Authors: Ma Ying-jie , Cao Xian-ling , Ma Ting , Song Jing-yan , Yu Ling-yu , Yu Yang-yang , Zhao Jian-Yun , Sun Zhen-Gao 
Published: September 2021

AbstractBackgroundInfertility is a widespread global challenge. Currently, the most effective treatment strategy for infertility is in vitro fertilization (IVF), which is an assisted reproductive technique (ART). The use of IVF for assisted pregnancy dates back to the last 41 years when the first IVF baby was born. During IVF, many oocytes are obtained in an IVF cycle, and more than one embryo is formed. Subsequently, frozen-thawed embryo transfer (FET) is increasingly being used in IVF cycles for women in whom a fresh embryo transfer fails to result in a pregnancy, or in those who return for a second baby. However, the pregnancy success rates following FET treatment cycles are reportedly lower than in fresh embryo transfers. Therefore, recent related studies are increasing determining mechanisms of improving the sustained pregnancy rate of FET and reducing the rate of early abortion.The Gushen’antai pill (GSATP), which contains a mixture of 10 herbs, has been widely used in traditional Chinese medicine (TCM) as a pharmacological option to prevent miscarriage. However, randomized controlled trials (RCT) have never been conducted to provide high-level clinical evidence on the clinical efficacy of GSATP. The objective of this study is to investigate the effect of GSATP of hormone therapy (HT) FET cycles on pregnancy rate.MethodsA total of 300 subjects aged between 18 and 40 years which prepared for HT cycle FET will be enrolled in the study. The patients were from five different hospitals, with 60 patients from each hospital. Patients were randomly divided into two groups, and medication was started on the day of endometrial transformation. After FET 28 days, B-ultrasound was done to determine whether to continue the medication. Baseline assessments were carried out before the trial and outcomes were collected 4, 6, 8, 10, and 12 weeks of each gestational cycle.DiscussionDifferences in ongoing pregnancy rate, clinical pregnancy rate, implantation rate, and threatened abortion rate between the two groups will be statistically analyzed. We can finally have an objective evaluation of the efficacy of the traditional Chinese medicine Gushen’antai pills.Trial registrationChiCTR1900026737. Registered October 20, 2019.
Effectiveness and cost-effectiveness of four different strategies for SARS-CoV-2 surveillance in the general population (CoV-Surv Study): study protocol for a two-factorial randomized controlled multi-arm trial with cluster sampling
Authors: Deckert Andreas , Anders Simon , De Allegri Manuela , Nguyen Hoa Thi , Souares Aurélia , McMahon Shannon , Meurer Matthias , Burk Robin , Sand Matthias , Koeppel Lisa , Hein Lena Maier , Roß Tobias , Adler Tim , Siems Tobias , Brugnara Lucia , Brenner Stephan , Herbst Konrad , Kirrmaier Daniel , Duan Yuanqiang , Ovchinnikova Svetlana , Boerner Kathleen , Marx Michael , Kräusslich Hans-Georg , Knop Michael , Bärnighausen Till , Denkinger Claudia 
Published: September 2021

Abstract
Background
To achieve higher effectiveness in population-based SARS-CoV-2 surveillance and to reliably predict the course of an outbreak, screening, and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic.

Methods
This trial implements a two-factorial, randomized, controlled, multi-arm, prospective, interventional, single-blinded design with cluster sampling and four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy based on individuals’ self-collection of saliva samples which are then sent to and analyzed by a laboratory. The targeted sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (2500 participants per arm). Strategies differ with respect to tested population groups (individuals vs. all household members) and testing approach (without vs. with pre-screening survey). The trial is complemented by an economic evaluation and qualitative assessment of user experiences. Primary outcomes include costs per completely screened person, costs per positive case, positive detection rate, and precision of positive detection rate.

Discussion
Systems for active surveillance of the general population will gain more importance in the context of pandemics and related disease prevention efforts. The pandemic parameters derived from such active surveillance with routine population monitoring therefore not only enable a prospective assessment of the short-term course of a pandemic, but also a more targeted and thus more effective use of local and short-term countermeasures.

Trial registration
ClinicalTrials.gov DRKS00023271. Registered November 30, 2020, with the German Clinical Trials Register (Deutsches Register Klinischer Studien)
Women’s experiences of receiving information about and consenting or declining to participate in a randomized controlled trial involving episiotomy in vacuum-assisted delivery: a qualitative study
Authors: Ericson Jenny , Anagrius Cecilia , Rygaard Agnes , Guntram Lisa , Wendel Sophia Brismar , Hesselman Susanne 
Published: September 2021

Abstract
Background
Information about and invitation to participate in a clinical trial involving an intervention during childbirth may cause fear or worry in pregnant women. The aim of this study was to describe nulliparous women’s experiences of receiving an invitation to participate in a randomized controlled trial (RCT) of lateral episiotomy versus no episiotomy in vacuum-assisted delivery (EVA trial).

Methods
This qualitative study was nested in the ongoing EVA trial. Data were collected through semistructured telephone interviews with 23 women regarding their experiences of the information and invitation to participate in the EVA trial. Interviews were audio-recorded and transcribed verbatim. A qualitative content analysis was used to analyse the interview contents.

Results
Three main experience categories were identified among the participants. “Timing of trial information and understanding” revealed that women preferred to obtain information about the trial early on during pregnancy. “Reasons to consent to or decline participation in the trial” encompassed a variety of reasons for women to consent, such as goodwill for science or personal benefits, or to decline, such as not wanting to be randomized or fear of increased risk of having a vacuum-assisted delivery. “Thoughts evoked regarding childbirth” were diverse, ranging from not being affected at all to having increased anxiety.

Conclusions
The women’s experience of receiving an invitation to participate in an RCT of episiotomy in vacuum-assisted delivery varied widely, from immediately giving consent without further worries to increased anxiety or declining participation. Early and personal information with time for reflection was considered most satisfactory.

Trial registration
ClinicalTrials.govNCT02643108. Registered on December 28, 2015. The Lateral Episiotomy or Not in Vacuum Assisted Delivery in Non-parous Women (EVA) trial was registered at www.clinicaltrials.gov.
Use of transcriptional age grading technique to determine the chronological age of Sri Lankan Aedes aegypti and Aedes albopictus females
Authors: Weeraratne Thilini Chathurika , Karunaratne S. H. P. Parakrama , Reimer Lisa , de Silva W. A. Priyanka P. , Wondji Charles S. 
Published: September 2021

Abstract
Background
Aedes aegypti and Ae. albopictus are important vectors of human diseases such as dengue, chikungunya, and zika. In Sri Lanka, they have been responsible for transmitting dengue virus. One of the most important parameters influencing the likelihood of arbovirus transmission is the age structure of the mosquito population. However, mosquito age is difficult to measure with accuracy. This study aims to construct multivariate calibration models using the transcriptional abundance of three age-responsive genes: Ae15848 (calcium-binding protein), Ae8505 (structural component of cuticle), and Ae4274 (fizzy cell cycle/cell division cycle 20).

Methods
The transcriptional age-grading technique was applied to determine the chronological age of Ae. aegypti and Ae. albopictus female mosquito populations from Sri Lanka using the age-responsive genes Ae15848, Ae8505, and Ae4274. Furthermore, Ae. aegypti samples obtained from colonies reared at two temperatures (23 and 27 °C) were used to investigate the influence of temperature on this age-grading technique. Expression levels of these three genes were quantified using reverse transcription qualitative PCR (qRT-PCR), and results were normalized against the housekeeping gene ribosomal gene S17 (RpS17).

Results
The expression of Ae15848 and Ae8505 decreased with the age of mosquitoes and showed the most significant and consistent change while expression of Ae4274 increased with age. The multivariate calibration models showed > 80% correlation between expression of these age-responsive genes and the age of female mosquitoes at both temperatures. At 27 °C the accuracy of age predictions using the models was 2.19 (± 1.66) days and 2.58 (± 2.06) days for Ae. aegypti and Ae. albopictus females, respectively. The accuracy of the model for Ae. aegypti at 23 °C was 3.42 (± 2.74) days.

Conclusions
An adult rearing temperature difference of 4 °C (23–27 °C) did not significantly affect the age predictions. The calibration models created during this study could be successfully used to estimate the age of wild Ae. aegypti and Ae. albopictus mosquitoes from Sri Lanka.

Graphical Abstract
Updated distribution of anopheline mosquitoes in Hokkaido, Japan, and the first evidence of Anopheles belenrae in Japan
Authors: Sawabe Kyoko , Imanishi-Kobayashi Nozomi , Maekawa Yoshihide , Higa Yukiko , Kim Kyeong Soon , Hoshino Keita , Tsuda Yoshio , Hayashi Toshihiko , Nihei Naoko , Takai Kenji , Kurihara Takeshi , Kobayashi Mutsuo 
Published: September 2021

Abstract
Background
In Hokkaido, northern island of Japan, at least seven cases of falciparum malaria were reported by 1951. A survey conducted at that time was unsuccessful in implicating any mosquito species as the possible vector. Although active anopheline mosquito surveillance continued until the middle of the 1980s, there is very limited information on their current status and distribution in Japan. Therefore, this study is an update on the current status and distribution of anopheline mosquitoes in Hokkaido based on a 15-year entomological surveillance between 2001 and 2015.

Methods
A survey of mosquitoes was conducted at 22 sites in Hokkaido, Japan, from 2001 to 2015. Adult mosquitoes were collected from cowsheds, lakesides, shrubs, and habitats ranging from open grassland to coniferous forest using a Centers for Disease Control and Prevention (CDC) miniature light trap enhanced with dry ice, aspirators, and sweeping nets. Larvae were collected from lakes, ponds, swamps, stagnant and flowing rivers, and paddy fields. All specimens were morphologically identified and subjected to polymerase chain reaction (PCR)-based sequence analysis of the internal transcribed spacer 2 ( ITS2) region of rDNA. Phylogenetic trees were reconstructed using the neighbor-joining method with the Kimura 2-parameter model on MEGA X version 10.2.2.

Results
A total of 46 anopheline specimens were used for the phylogenetic analysis. During the survey, a new member of the Anopheles hyrcanus group, An. belenrae, was discovered in eastern Hokkaido in 2004. Anopheles belenrae has since then been consistently found and confirmed to inhabit only this area of Japan. Four members of the An. hyrcanus group, namely An. belenrae, An. engarensis, An. lesteri, and An. sineroides, have been found in Hokkaido. The results also suggest that An. sinensis, formerly a dominant species throughout Japan, has become a rarely found species, at least currently in Hokkaido.

Conclusion
The updated distribution of anopheline mosquitoes in Hokkaido, Japan, showed considerable differences from that observed in previous surveys conducted from 1969 to 1984. In particular, areas where An. sinensis was previously distributed may have been greatly reduced in Hokkaido. The phylogenetic analysis revealed a novel An. hyrcanus group member identified as An. belenrae, described in South Korea in 2005. It is interesting that An. belenrae was confirmed to inhabit only eastern Hokkaido, Japan.

Graphical abstract
Assessing the anti-resistance potential of public health vaporizer formulations and insecticide mixtures with pyrethroids using transgenic Drosophila lines
Authors: Luong Hang Ngoc Bao , Damijonaitis Arunas , Nauen Ralf , Vontas John , Horstmann Sebastian 
Published: September 2021

Abstract
Background
Insecticide resistance—and especially pyrethroid resistance—is a major challenge for vector control in public health. The use of insecticide mixtures utilizing alternative modes of action, as well as new formulations facilitating their uptake, is likely to break resistance and slow the development of resistance.

Methods
We used genetically defined highly resistant lines of Drosophila melanogaster with distinct target-site mutations and detoxification enzymes to test the efficacy and anti-resistance potential of novel mixture formulations (i.e. Fludora® Fusion consisting of deltamethrin and clothianidin), as well as emulsifiable concentrate transfluthrin, compared to alternative, currently used pyrethroid insecticide formulations for vector control.

Results
The commercial mixture Fludora® Fusion, consisting of both a pyrethroid (deltamethrin) and a neonicotinoid (clothianidin), performed better than either of the single active ingredients against resistant transgenic flies. Transfluthrin, a highly volatile active ingredient with a different molecular structure and primary exposure route (respiration), was also efficient and less affected by the combination of metabolic and target-site resistance. Both formulations substantially reduced insecticide resistance across different pyrethroid-resistant Drosophila transgenic strains.

Conclusions
The use of mixtures containing two unrelated modes of action as well as a formulation based on transfluthrin showed increased efficacy and resistance-breaking potential against genetically defined highly resistant Drosophila flies. The experimental model remains to be validated with mosquito populations in the field. The possible introduction of new transfluthrin-based products and mixtures for indoor residual spraying, in line with other combination and mixture vector control products recently evaluated for use in public health, will provide solutions for better insecticide resistance management.

Graphical abstract
Population genetic structure of the malaria vector Anopheles minimus in Thailand based on mitochondrial DNA markers
Authors: Bunmee Kamonchanok , Thaenkham Urusa , Saralamba Naowarat , Ponlawat Alongkot , Zhong Daibin , Cui Liwang , Sattabongkot Jetsumon , Sriwichai Patchara 
Published: September 2021

Abstract
Background
The malaria vector Anopheles minimus has been influenced by external stresses affecting the survival rate and vectorial capacity of the population. Since An. minimus habitats have continuously undergone ecological changes, this study aimed to determine the population genetic structure and the potential gene flow among the An. minimus populations in Thailand.

Methods
Anopheles minimus was collected from five malaria transmission areas in Thailand using Centers for Disease Control and Prevention (CDC) light traps. Seventy-nine females from those populations were used as representative samples. The partial mitochondrial cytochrome c oxidase subunit I (COI), cytochrome c oxidase subunit II (COII) and cytochrome b (Cytb) gene sequences were amplified and analyzed to identify species and determine the current population genetic structure. For the past population, we determined the population genetic structure from the 60 deposited COII sequences in GenBank of An. minimus collected from Thailand 20 years ago.

Results
The current populations of An. minimus were genetically divided into two lineages, A and B. Lineage A has high haplotype diversity under gene flow similar to the population in the past. Neutrality tests suggested population expansion of An. minimus, with the detection of abundant rare mutations in all populations, which tend to arise from negative selection.

Conclusions
This study revealed that the population genetic structure of An. minimus lineage A was similar between the past and present populations, indicating high adaptability of the species. There was substantial gene flow between the eastern and western An. minimus populations without detection of significant gene flow barriers.

Graphical abstract
Granulocytic myeloid-derived suppressor cells inhibit T follicular helper cells during experimental Schistosoma japonicum infection
Authors: Zhang Yumei , Wu Yulong , Liu Hua , Gong Wenci , Hu Yuan , Shen Yujuan , Cao Jianping 
Published: September 2021

AbstractBackgroundCD4+T helper (Th) cells play critical roles in both host humoral and cellular immunity against parasitic infection and in the immunopathology of schistosomiasis. T follicular helper (Tfh) cells are a specialized subset of Th cells involved in immunity against infectious diseases. However, the role of Tfh cells in schistosome infection is not fully understood. In this study, the dynamics and roles of Tfh cell regulation were examined. We demonstrated that granulocytic myeloid-derived suppressor cells (G-MDSC) can suppress the proliferation of Tfh cells.MethodsThe levels of Tfh cells and two other Th cells (Th1, Th2) were quantitated at differentSchistosoma japonicuminfection times (0,3, 5, 8, 13 weeks) using flow cytometry. The proliferation of Tfh cells stimulated by soluble egg antigen (SEA) and soluble worm antigen (SWA) in vivo and in vitro were analyzed. Tfh cells were co-cultured with MDSC to detect the proliferation of Tfh cells labelled by 5(6)-carboxyfluorescein diacetateN-succinimidyl ester. We dynamically monitored the expression of programmed cell death protein 1 (PD-1) on the surface of Tfh cells and programmed cell death ligand 1 (PD-L1) on the surface of MDSC at different infection times (0, 3, 5, 8 weeks). Naïve CD4+T cells (in Tfh cell differentiation) were co-cultured with G-MDSC or monocytic MDSC in the presence, or in the absence, of PD-L1 blocking antibody.ResultsThe proportion of Tfh cells among CD4+T cells increased gradually with time ofS. japonicuminfection, reaching a peak at 8 weeks, after which it decreased gradually. Both SEA and SWA caused an increase in Tfh cells in vitro and in vivo. It was found that MDSC can suppress the proliferation of Tfh cells. The expression of PD-1 on Tfh cells and PD-L1 from MDSC cells increased with prolongation of the infection cycle. G-MDSC might regulate Tfh cells through the PD-1/PD-L1 pathway.ConclusionsThe reported study not only reveals the dynamics of Tfh cell regulation duringS. japonicuminfection,but also provides evidence that G-MDSC may regulate Tfh cells by PD-1/PD-L1. This study provides strong evidence for the important role of Tfh cells in the immune response toS. japonicuminfection.Graphical abstract