bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial
Authors: Song Zhengbo , Li Yuping , Chen Shiqing , Ying Shenpeng , Xu Shuguang , Huang Jianjin , Wu Dan , Lv Dongqing , Bei Ting , Liu Shuxun , Huang Xiaoping , Xie Congying , Wu Xiaoyu , Fu Jianfei , Hua Feng , Wang Wenxian , Xu Chunwei , Gao Chan , Cai Shangli , Lu Shun , Zhang Yiping 
Published: February 2022

Abstract
Background
There is currently a lack of effective treatments for non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. We examined the efficacy and safety of, and potential resistance mechanism to, pyrotinib, a pan-HER inhibitor, in advanced NSCLC carrying HER2 mutations.

Methods
In this multicenter, single-arm, phase II trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day. The primary endpoint was 6-month progression-free survival (PFS) rate, and secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety. The impact of different HER2 mutation types on sensitivity to pyrotinib and the potential of utilizing mutational profile derived from circulating tumor DNA (ctDNA) to predict disease progression were also explored.

Results
Seventy-eight patients were enrolled for efficacy and safety analysis. The 6-month PFS rate was 49.5% (95% confidence interval [CI], 39.2–60.8). Pyrotinib produced an ORR of 19.2% (95% CI, 11.2–30.0), with median PFS of 5.6 months (95% CI, 2.8–8.4), and median OS of 10.5 months (95% CI, 8.7–12.3). The median duration of response was 9.9 months (95% CI, 6.2–13.6). All treatment-related adverse events (TRAEs) were grade 1–3 (all, 91.0%; grade 3, 20.5%), and the most common TRAE was diarrhea (all, 85.9%; grade 3, 16.7%). Patients with exon 20 and non-exon 20 HER2 mutations had ORRs of 17.7% and 25.0%, respectively. Brain metastases at baseline and prior exposure to afatinib were not associated with ORR, PFS, or OS. Loss of HER2 mutations and appearance of amplification in HER2 and EGFR were detected upon disease progression.

Conclusions
Pyrotinib exhibited promising efficacy and acceptable safety in NSCLC patients carrying exon 20 and non-exon 20 HER2 mutations and is worth further investigation.

Trial registration
Chinese Clinical Trial Registry Identifier: ChiCTR1800020262
A novel missense variant in ESRRB gene causing autosomal recessive non-syndromic hearing loss: in silico analysis of a case
Authors: Ghasemnejad Tohid , Shekari Khaniani Mahmoud , Nouri Nojadeh Jafar , Mansoori Derakhshan Sima 
Published: February 2022

Abstract
Background
Hereditary hearing loss (HHL) is a common heterogeneous disorder affecting all ages, ethnicities, and genders. The most common form of HHL is autosomal recessive non-syndromic hearing loss (ARNSHL), in which there is no genotype–phenotype correlation in the majority of cases. This study aimed to identify the genetic causes of hearing loss (HL) in a family with Iranian Azeri Turkish ethnicity negative for gap junction beta-2 (GJB2), gap junction beta-6 (GJB6), and mitochondrially encoded 12S rRNA (MT-RNR1) deleterious mutations.

Methods
Targeted genome sequencing method was applied to detect genetic causes of HL in the family. Sanger sequencing was employed to verify the segregation of the variant. Finally, we used bioinformatics tools and American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines to determine whether the detected variant might affect the corresponding protein or not.

Results
A novel homozygous missense mutation, c.499G>A (p.G167R), was identified in exon 5 of the ESRRB (estrogen-related receptor beta) gene. Healthy and affected family members confirmed the co-segregation of the variant with ARNSHL. Eventually, the variant's pathogenicity was confirmed by the in silico analysis and the ACMG/AMP guidelines.

Conclusion
The study suggests that the detected variant, c.499G>A, plays a crucial role in the development of ARNSHL, emphasizing the clinical significance of the ESRRB gene in ARNSHL patients. Additionally, it would be helpful for genetic counseling and clinical management of ARNSHL patients and providing preventive opportunities.
Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation
Authors: Wink Lily , Miller Richard A. , Garcia Gonzalo G. 
Published: February 2022

Abstract
Background
Rapamycin (Rapa), acarbose (ACA), and 17α-estradiol (17aE2, males only) have health benefits that increase lifespan of mice. Little is known about how these three agents alter the network of pathways downstream of insulin/IGF1 signals as well as inflammatory/stress responses.

Results
ACA, Rapa, and 17aE2 (in males, but not in females) oppose age-related increases in the MEK1- ERK1/2-MNK1/2 cascade, and thus reduce phosphorylation of eIF4E, a key component of cap-dependent translation. In parallel, these treatments (in both sexes) reduce age-related increases in the MEK3-p38MAPK-MK2 pathway, to decrease levels of the acute phase response proteins involved in inflammation.

Conclusion
Each of three drugs converges on the regulation of both the ERK1/2 signaling pathway and the p38-MAPK pathway. The changes induced by treatments in ERK1/2 signaling are seen in both sexes, but the 17aE2 effects are male-specific, consistent with the effects on lifespan. However, the inhibition of age-dependent p38MAPK pathways and acute phase responses is triggered in both sexes by all three drugs, suggesting new approaches to prevention or reversal of age-related inflammatory changes in a clinical setting independent of lifespan effects.
Three cases of macular hole that occurred in inferior scleral staphyloma associated with tilted disc syndrome: a case series
Authors: Mizuno Hiroshi , Suzuki Hiroyuki , Mimura Masashi , Fukumoto Masanori , Sato Takaki , Kida Teruyo , Ikeda Tsunehiko 
Published: February 2022

Abstract
Background
The objective is to examine the clinical characteristics of three patients with macular hole that occurred in inferior posterior staphyloma associated with tilted disc syndrome.

Case presentations
This study involved three eyes of three Japanese female patients (mean age 76.0 years, range 73–84 years) with macular hole occurring in inferior posterior staphyloma associated with tilted disc syndrome. One of the three eyes was slightly myopic, while the other two eyes were highly myopic. In all three eyes, the macular hole was found to be located in or near the margin of the inferior posterior staphyloma. In one eye, the extent of retinoschisis was rather broad in the margin of the macular hole, and another eye had a history of treatment for choroidal neovascularization. As surgical treatment, the internal limiting membrane in areas surrounding the macular hole was detached after producing artificial posterior vitreous detachment, and a gas tamponade was performed. It was found during surgery that the extensibility of the retina in the margin of the MH was decreased in the three eyes as compared with a usual macular hole. Although the macular hole was successfully closed in all three cases post surgery, the layer structure of the central retina was poorly repaired in all three cases and choroidal neovascularization remained in one case. In all three cases, corrected visual acuity remained at 0.3–0.5 post surgery.

Conclusions
Our findings showed poor improvement of visual acuity in all three cases post surgery, even if closure of the macular hole is achieved, thus suggesting that in cases of macular hole associated with tilted disc syndrome and inferior posterior staphyloma, the presence of macular dysfunction existing prior to the onset of macular hole affects visual prognosis.
Mini-implant assisted rapid palatal expansion (MARPE) effects on adult obstructive sleep apnea (OSA) and quality of life: a multi-center prospective controlled trial
Authors: Brunetto Daniel Paludo , Moschik Christoph E. , Dominguez-Mompell Ramon , Jaria Eliza , Sant’Anna Eduardo Franzotti , Moon Won 
Published: February 2022

Abstract
Introduction
Transverse maxillary deficiency is a high prevalent growth disorder within the adult population that may lead to serious health issues, such as detrimental malocclusions and higher risk of developing obstructive sleep apnea (OSA). Mini-implant assisted rapid palatal expansion (MARPE), as it expands the mid-face and augment the nasal and oral cavities dimensions, may reduce the airflow resistance and thus play an important role on OSA therapy in some patients. The main objective of the present trial is to assess MARPE effects on the sleep and quality of life of non-obese adult OSA patients with transverse maxillary deficiency.

Methods
A total of 32 participants were divided into intervention and control groups. They underwent physical evaluation, Epworth Sleepiness Scale (EES) and Quebec Sleep Questionnaire (QSQ), cone-beam computed tomography (CBCT) and home sleep testing (HST) for OSA before MARPE (T1) and 6 months after the intervention (T2).

Results
Questionnaires EES (daytime sleepiness) and QSQ (OSA-related quality of life) presented significant statistical differences between the groups. We also found clinical and statistical (p < 0.01) differences between the groups regarding the apnea/hypopnea index (AHI), as well as others HST parameters (mean oxygen saturation and snoring duration).

Conclusion
In our sample, MARPE (without any auxiliary osteotomy) showed a good success rate (85%) and promoted important occlusal and respiratory benefits. We observed important daytime sleepiness and OSA-related quality of life improvement, as well as the AHI (65.3%), oxygen saturation and snoring duration.
Three myths of disseminating COVID-19 information to vulnerable migrants in Japan: lessons learned during the pandemic
Authors: Kiyohara Hiroyuki , Teshima Yuko , Hoshino Haru Angelique , Kanda Miwa , Matsuoka Sadatoshi , Iwamoto Azusa , Fujita Masami 
Published: February 2022

AbstractThis paper discusses the challenges of disseminating COVID-19 information to migrant populations by sharing our trial-and-error approach. In 2018, the Migrants’ Neighbor Network & Action (MINNA), a consortium of individuals and organizations that addressed the issues of accessing relevant information and services for migrants in Japan, was launched. Amidst the COVID-19 pandemic, the MINNA attempted to investigate and improve access to health information among Vietnamese, Nepali, and Burmese migrants in Japan. We had three assumptions in distribution of information to reach a large audience, such as building a multilingual website, requesting stakeholders to disseminate information, or posting on Facebook. None of our assumptions were sufficient to reach the target audience in the context of COVID-19, as total number of views that accessed our materials were less than 300 at most. We viewed these myths as the result of overlooking critical elements of effective communication strategies. Eventually, MINNA managed to establish communication with the manager of a Facebook page with the largest number of followers from the Vietnamese community in Japan. Compared with our previous attempts, the messages were delivered to a large audience on the Facebook page, such as the article on COVID-19 vaccines that was viewed more than 300,000 times. In public health emergencies, interactive process of information dissemination is necessary. It is a key component for risk communication and should be prioritized. Breakthroughs in communicating with a larger audience could be possible through partnerships with online communities.
Interpretation of regulatory factors for 3D printing at hospitals and medical centers, or at the point of care
Authors: Beitler Brian G. , Abraham Paul F. , Glennon Alyssa R. , Tommasini Steven M. , Lattanza Lisa L. , Morris Jonathan M. , Wiznia Daniel H. 
Published: February 2022

Abstract3D printing is revolutionizing the medical device landscape through its ability to rapidly create patient-specific anatomic models, surgical instruments, and implants. Recent advances in 3D printing technology have allowed for the creation of point-of-care (PoC) 3D printing centers. These PoC centers blur the line between healthcare provider, medical center, and device manufacturer, creating regulatory ambiguity. The United States Food & Drug Administration (FDA) currently regulates 3D printed devices through existing medical device regulations. However, the FDA is increasingly interested in developing guidelines and regulations specifically for PoC 3D printing due to its rapid adoption across the healthcare institutions. In this article, we review the regulatory framework that governs medical devices, discuss how PoC 3D printing falls within this framework, and describe a novel conceptual framework that the FDA has proposed. Finally, through analysis of the aforementioned regulations and discussions with industry medical 3D printing regulatory experts, we provide recommendations for PoC medical 3D printing best practices so that institutions are best positioned to utilize this revolutionary technology safely and effectively.
A novel prostaglandin I2 agonist, ONO-1301, attenuates liver inflammation and suppresses fibrosis in non-alcoholic steatohepatitis model mice
Authors: Motegi Satoko , Tsuchiya Atsunori , Iwasawa Takahiro , Sato Takeki , Kumagai Masaru , Natsui Kazuki , Nojiri Shunsuke , Ogawa Masahiro , Takeuchi Suguru , Sakai Yosiki , Miyagawa Shigeru , Sawa Yoshiki , Terai Shuji 
Published: February 2022

Abstract
Background
ONO-1301 is a novel long-lasting prostaglandin (PG) I2 mimetic with inhibitory activity on thromboxane (TX) A2 synthase. This drug can also induce endogenous prostaglandin (PG)I2 and PGE2 levels. Furthermore, ONO-1301 acts as a cytokine inducer and can initiate tissue repair in a variety of diseases, such as pulmonary hypertension, pulmonary fibrosis, cardiac infarction, and obstructive nephropathy. In this study, our aim was to evaluate the effect of ONO-1301 on liver inflammation and fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH).

Methods
The therapeutic effects of ONO-1301 against liver damage, fibrosis, and occurrence of liver tumors were evaluated using melanocortin 4 receptor-deficient (Mc4r-KO) NASH model mice. The effects of ONO-1301 against macrophages, hepatic stellate cells, and endothelial cells were also evaluated in vitro.

Results
ONO-1301 ameliorated liver damage and fibrosis progression, was effective regardless of NASH status, and suppressed the occurrence of liver tumors in Mc4r-KO NASH model mice. In the in vitro study, ONO-1301 suppressed LPS-induced inflammatory responses in cultured macrophages, suppressed hepatic stellate cell (HSC) activation, upregulated vascular endothelial growth factor (VEGF) expression in HSCs, and upregulated hepatocyte growth factor (HGF) and VEGF expression in endothelial cells.

Conclusions
The results of our study highlight the potential of ONO-1301 to reverse the progression and prevent the occurrence of liver tumors in NASH using in vivo and in vitro models. ONO-1301 is a multidirectional drug that can play a key role in various pathways and can be further analyzed for use as a new drug candidate against NASH.
Impact of gene polymorphism of glutathione S-transferase and ghrelin as a risk factor in Egyptian women with gestational diabetes mellitus
Authors: Madkour Mai M. , El-Said Afaf M. , El-Refaey Abd El-Aziz A. , Abd El-Aziz Abd El-Aziz F. , El-Senduny Fardous F. 
Published: February 2022

AbstractBackgroundGestational diabetes mellitus is the most common metabolic dysfunction that arises during pregnancy. GDM can lead to serious health complications for both the mother during pregnancy and after the delivery of the baby. Additionally, mother–offspring suffers from abnormalities in metabolism. The study aimed to investigateglutathione S‑transferase P1andghrelingenetic variants in pregnant women diagnosed with gestational diabetes using a tetra-primer amplification refractory mutation system.ResultsThis study demonstrated that the frequencies of genotypes in women with GDM were GSTP1-AG (87.1%) and GHRL-GG (100%). The study revealed no significant differences in the frequency of either genotype or allele of bothGSTP1andghrelinbetween GDM and healthy pregnant women.ConclusionsThis study may be the first study designed to demonstrate that there is no association between the genotype and allele frequencies ofGSTP1(rs1695) andghrelin(rs696217) in the development of gestational diabetes mellitus in Egyptian women.
Another indication for a transanal pull-through: surgical management of rectal atresia—a case report
Authors: Akkary Rezkalla , Diab Nabil , Zeidan Smart 
Published: February 2022

Abstract
Background
Rectal atresia is a very rare cause of neonatal intestinal obstruction. It has some distinctive anatomical and physiological specifications. The management is controversial with many described operative techniques. In this case report, we described our patient that we operated according to the transanal pull-through technique. We discussed the advantages and disadvantages of this technique and what makes it a suitable option for this population of patient.

Case presentation
A full-term male patient presented at 36 h of life for a pneumoperitoneum. Because of his well-placed, normally appearing anus, the diagnosis of rectal atresia was delayed. The patient was operated then according to the transanal pull-through technique with good follow-up results.

Conclusion
Transanal pull-through is a safe, easy. and a potentially reproducible option for managing rectal atresia. It should be considered for managing future cases. More cases should be done before drawing big conclusions.
Notch signaling is a novel regulator of visceral smooth muscle cell differentiation in the murine ureter
Authors: Kurz Jennifer , Weiss Anna-Carina , Thiesler Hauke , Qasrawi Fairouz , Deuper Lena , Kaur Jaskiran , Rudat Carsten , Lüdtke Timo H. , Wojahn Irina , Hildebrandt Herbert , Trowe Mark-Oliver , Kispert Andreas 
Published: February 2022

ABSTRACT
The contractile phenotype of smooth muscle cells (SMCs) is transcriptionally controlled by a complex of the DNA-binding protein SRF and the transcriptional co-activator MYOCD. The pathways that activate expression of Myocd and of SMC structural genes in mesenchymal progenitors are diverse, reflecting different intrinsic and extrinsic signaling inputs. Taking the ureter as a model, we analyzed whether Notch signaling, a pathway previously implicated in vascular SMC development, also affects visceral SMC differentiation. We show that mice with a conditional deletion of the unique Notch mediator RBPJ in the undifferentiated ureteric mesenchyme exhibit altered ureter peristalsis with a delayed onset, and decreased contraction frequency and intensity at fetal stages. They also develop hydroureter 2 weeks after birth. Notch signaling is required for precise temporal activation of Myocd expression and, independently, for expression of a group of late SMC structural genes. Based on additional expression analyses, we suggest that a mesenchymal JAG1-NOTCH2/NOTCH3 module regulates visceral SMC differentiation in the ureter in a biphasic and bimodal manner, and that its molecular function differs from that in the vascular system.
Policy Brief 3: Social norms, mental models and other behavioural drivers of petty corruption
Authors: Baez Camargo Claudia , Kassa Saba , Stahl Cosimo 
Published: February 2022

This Policy Brief summarises the main findings and lessons learned from a research on corruption, social norms and behaviours in Rwanda. The findings show that, although Rwanda has successfully curbed corruption, favouritism continues to be used to secure preferential access to public health services.
While the Rwandan experience illustrates how behavioural insights can effectively complement conventional anti-corruption approaches, further entry areas for deepening behavioural anti-corruption interventions are also identified.
Policy Brief 5: Curbing wildlife trafficking in Uganda
Authors: Kassa Saba , Costa Jacopo , Lugolobi Robert , Baez Camargo Claudia 
Published: February 2022

This policy brief summarises the main findings from extensive field research on the drivers, facilitators and strategies of wildlife trafficking in Uganda. It translates the insights described in Working Paper 33: A worm’s-eye view of wildlife trafficking in Uganda into recommendations for practitioners and policymakers.
The research shows that individuals engaging in the first stages of the trading route are driven predominantly by aspirations of wealth to overcome socio-economic hardships. This is reinforced by stereotypes that depict wildlife trade as benign and legitimate.
The trafficking is also facilitated by weak governance systems that generate high levels of corruption and impunity. In such a context, opportunistic strategies sustain the operations of organised transnational wildlife trafficking networks, not least because of the availability of a ready pool of accomplices who can be co-opted to facilitate the effective consolidation, concealment and corrupt cover of high volumes of wildlife products.
Policymakers who wish to reduce the attractiveness of Uganda for organised wildlife trafficking networks are advised to consider these factors when designing their interventions.
This report was funded by PMI IMPACT, a grant award initiative of Philip Morris International (PMI). In the performance of their research, the authors maintained full independence from PMI. The views and opinions expressed in this document are those of the authors and do not necessarily reflect the views of PMI. Neither PMI, nor any of its affiliates, nor any person acting on their behalf may be held responsible for any use which may be made of the information contained herein.
Policy Brief 8: It takes a network to defeat a network – What Collective Action practitioners can learn from research into corrupt networks
Authors: Baez Camargo Claudia , Costa Jacopo , Hans Vanessa , Koechlin Lucy , Wannenwetsch Scarlet 
Published: February 2022

This Policy Brief distils recommendations for Collective Action practitioners based on empirical insights on certain forms of corruption involving private-sector actors.
Field research carried out in Tanzania and Uganda produced detailed case studies that show how informal networks link private and public sector actors to pursue common illicit goals, such as gaining an unfair business advantage, avoiding a sanction, decreasing taxes owed or jumping the queue at the point of delivery of public services. Corruption, most often bribery, is the currency that works to cement and nurture those networks.
This Policy Brief is based on that research and a series of in-depth interviews with Collective Action practitioners working in Africa, Eastern Europe and Latin America. The goal is to extract insights from what we have learned about the networks that fuel corruption and discuss implications for anti-corruption Collective Action initiatives.