bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsupervised Resolution of Histomorphologic Heterogeneity in Renal Cell Carcinoma Using a Brain Tumor–Educated Neural Network
Authors: Faust Kevin , Roohi Adil , Leon Alberto J. , Leroux Emeline , Dent Anglin , Evans Andrew J. , Pugh Trevor J. , Kalimuthu Sangeetha N. , Djuric Ugljesa , Diamandis Phedias 
Published: September 2020

PURPOSE Applications of deep learning to histopathology have proven capable of expert-level performance, but approaches have largely focused on supervised classification tasks requiring context-specific training and deployment. More generalizable workflows that can be easily shared across subspecialties could help accelerate and broaden adoption. Here, we hypothesized that histology-optimized feature representations, generated by a convolutional neural network (CNN) during supervised learning, are transferable and can resolve meaningful differences in large-scale, discovery-type unsupervised analyses. METHODS We used a CNN, previously trained to recognize brain tumor histomorphologies, to extract 512 feature representations from > 550 digital whole-slide images (WSIs) of renal cell carcinomas (RCCs) from The Cancer Genome Atlas and other previously unencountered tumors. We use these extracted feature vectors to conduct unsupervised image-set clustering and analyze the clinical and biologic relevance of the intra- and interpatient subgroups generated. RESULTS Within individual WSIs, feature-based clustering could reliably segment tumor regions and other relevant histopathologic subpatterns (eg, adenosquamous and poorly differentiated regions). Across the larger RCC cohorts, clustering extracted features generated subgroups enriched for clinically relevant subtypes (eg, papillary RCC) and outcomes (eg, survival). Importantly, individual feature activation mapping highlighted salient subtype-specific patterns and features of malignancies (eg, nuclear grade, sarcomatous change) contributing to subgroupings. Moreover, some proposed clusters were enriched for recurring, human-based RCC-subtype misclassifications. CONCLUSION Our data support that CNNs, pretrained on large histologic datasets, can extend learned representations to novel scenarios and resolve clinically relevant intra- and interpatient tissue-pattern differences without explicit instruction or additional optimization. Repositioning of existing histology-educated networks could provide scalable approaches for image classification, quality assurance, and discovery of unappreciated patterns and subgroups of disease.
Disrupted Hypothalamo-Pituitary Axis in Association With Reduced SHH Underlies the Pathogenesis of NOTCH-Deficiency
Authors: Hamdi-Rozé Houda , Ware Michelle , Guyodo Hélène , Rizzo Aurélie , Ratié Leslie , Rupin Maïlys , Carré Wilfrid , Kim Artem , Odent Sylvie , Dubourg Christèle , David Véronique , de Tayrac Marie , Dupé Valérie 
Published: September 2020

AbstractContextIn human, Sonic hedgehog (SHH) haploinsufficiency is the predominant cause of holoprosencephaly, a structural malformation of the forebrain midline characterized by phenotypic heterogeneity and incomplete penetrance. The NOTCH signaling pathway has recently been associated with holoprosencephaly in humans, but the precise mechanism involving NOTCH signaling during early brain development remains unknown.ObjectiveThe aim of this study was to evaluate the relationship between SHH and NOTCH signaling to determine the mechanism by which NOTCH dysfunction could cause midline malformations of the forebrain.DesignIn this study, we have used a chemical inhibition approach in the chick model and a genetic approach in the mouse model. We also reported results obtained from the clinical diagnosis of a cohort composed of 141 holoprosencephaly patients.ResultsWe demonstrated that inhibition of NOTCH signaling in chick embryos as well as in mouse embryos induced a specific downregulation of SHH in the anterior hypothalamus. Our data in the mouse also revealed that the pituitary gland was the most sensitive tissue to Shh insufficiency and that haploinsufficiency of the SHH and NOTCH signaling pathways synergized to produce a malformed pituitary gland. Analysis of a large holoprosencephaly cohort revealed that some patients possessed multiple heterozygous mutations in several regulators of both pathways.ConclusionsThese results provided new insights into molecular mechanisms underlying the extreme phenotypic variability observed in human holoprosencephaly. They showed how haploinsufficiency of the SHH and NOTCH activity could contribute to specific congenital hypopituitarism that was associated with a sella turcica defect.
Pharmacodynamic Activity of the Novel Neurokinin-3 Receptor Antagonist SJX-653 in Healthy Men
Authors: Anderson Richard A , Cormier Jennifer , Thieroff-Ekerdt Ruth , Boyce Malcolm , van den Berg Frans , Grau Daniel , Turnquist David , Corzo Deya , Graham Philip 
Published: September 2020

Abstract

Context
SJX-653 is a novel neurokinin 3 receptor (NK3R) antagonist. The NK3 pathway is a central regulator of gonadotropin releasing hormone (GnRH) secretion and has also been implicated in the generation of hot flashes. Therefore, decreases of luteinizing hormone (LH) and testosterone in men serve as sensitive pharmacodynamic (PD) markers of central NK3 antagonism.

Objective
To characterize the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of SJX-653 in healthy men.

Design
A randomized, placebo-controlled, double-blind, single ascending dose study.

Setting
Phase 1 unit.

Patients or Other Participants
Seven cohorts of 6 healthy men 18–45 years of age (4:2 randomization to SJX-653/placebo per cohort).

Intervention(s)
Single oral doses of 0.5–90 mg SJX-653.

Main Outcome Measure(s)
Safety assessments and serial pharmacokinetic (PK)/PD measurements.

Results
SJX-653 was well tolerated at all dose levels. Cmax and AUC0-24 increased in a dose-proportional manner. The terminal elimination half-life ranged between 9.8 and 12.5 hours independent of dose. A statistically significant, dose-dependent, reversible reduction of LH and testosterone was observed with near maximal effect after 15 mg and little to no effect at 4.5 mg. Maximal LH reduction was 70 ± 7% (mean ± sd) at 6 hours after 30 mg SJX-653 versus 10 ± 43% for placebo (P = 0.0006); maximal T reduction was of 68 ± 5% at 8 hours after 60 mg SJX-653 versus 18 ± 11% for placebo (P &lt; 0.0001). The plasma IC50 for LH reduction was 33 ng/mL.

Conclusions
These data demonstrate clinical proof-of-mechanism for SJX-653 as a potent centrally-acting NK3R antagonist.
Surgical and Pharmacological Outcomes in Acromegaly: Real-Life Data From the Mexican Acromegaly Registry
Authors: Mercado Moisés , Abreu Coralys , Vergara-López Alma , González-Virla Baldomero , Espinosa-de-los-Monteros Ana-Laura , Sosa-Eroza Ernesto , Cadena-Obando Diego , Cuevas-Ramos Daniel , Portocarrero-Ortiz Lesly A , Pérez-Reyes Sara-Patricia , Mercado-Cherem Abraham , Ibarra-Salce Raúl , Talavera Juan O 
Published: September 2020

Abstract

Context
Acromegaly registries constitute a valuable source of therapeutic outcome information in real-life.

Objective
The objective of this work is to analyze surgical and pharmacological outcomes in the Mexican Acromegaly Registry (MAR).

Design and Methods
Data were extracted from the MAR informatic platform. Surgical remission was defined by a postoperative postglucose (GH) of less than 1 ng/mL and an insulin-like growth factor 1 (IGF-1) of less than 1.2 × upper limit of normal (ULN). Pharmacological remission was defined by a basal GH of less than 1 ng/mL and an IGF-1 of less than 1.2 × ULN.

Results
A total of 650 surgical outcomes were analyzed (94.6% transsphenoidal). Surgical remission was achieved in 40.15%, whereas 44.15% remained biochemically active. Persistently active disease after surgery was significantly associated with harboring an invasive macroadenoma, a basal GH of greater than 10 ng/mL, and/or an IGF-1 of greater than 2 × ULN at diagnosis on bivariate and multivariate analysis. The outcome of monotherapy with first-generation somatostatin analogs (SSAs) was evaluated in 267 patients (adjunctive in 65%), of whom 28.4% achieved remission. Persistently active disease was significantly associated with harboring an invasive macroadenoma as well as with pretreatment basal GH and IGF-1 levels of greater than 10 ng/mL and greater than 2 × ULN, respectively, on bivariate and multivariate analysis. Combined therapy with SSA and cabergoline was analyzed in 100 patients, of whom 19% achieved remission and 44% remained active; in this subset of patients, only a pretreatment IGF-1 of greater than 2 × ULN was significantly associated with persistent disease activity.

Conclusion
Surgical and pharmacological outcomes in acromegaly are highly dependent on tumor size/invasiveness as well as on the degree of hypersomatotropinemia.
Tracking and forecasting milepost moments of the epidemic in the early-outbreak: framework and applications to the COVID-19
Authors: Wang Huiwen , Zhang Yanwen , Lu Shan , Wang Shanshan 
Published: September 2020

Background: The outbreak of the 2019 novel coronavirus (COVID-19) has attracted global attention. In the early stage of the outbreak, the most important question concerns some meaningful milepost moments, including the time when the number of daily confirmed cases decreases, the time when the number of daily confirmed cases becomes smaller than that of the daily removed (recovered and death), and the time when the number of daily confirmed cases and patients treated in hospital, which can be called “active cases”, becomes zero. Unfortunately, it is extremely difficult to make right and precise prediction due to the limited amount of available data at the early stage of the outbreak. To address it, in this paper, we propose a flexible framework incorporating the effectiveness of the government control to forecast the whole process of a new unknown infectious disease in its early-outbreak. Methods: We first establish the iconic indicators to characterize the extent of epidemic spread. Then we develop the tracking and forecasting procedure with mild and reasonable assumptions. Finally we apply it to analyze and evaluate the COVID-19 outbreak using the public available data for mainland China beyond Hubei Province from the China Centers for Disease Control (CDC) during the period of Jan 29th, 2020, to Feb 29th, 2020, which shows the effectiveness of the proposed procedure. Results: Forecasting results indicate that the number of newly confirmed cases will become zero in the mid-early March, and the number of patients treated in the hospital will become zero between mid-March and mid-April in mainland China beyond Hubei Province. Conclusions: The framework proposed in this paper can help people get a general understanding of the epidemic trends in countries where COVID-19 are raging as well as any other outbreaks of new and unknown infectious diseases in the future.
Analysis of evidence in forensic medicine. Validation of the test method as a tool to control parameters determining the reliability of the analysis results
Authors: Szczęśniak Angelika , Serwin Natalia , Cecerska-Heryć Elżbieta , Stangret Anna , Mularczyk Agata , Grzeszczak Konrad , Topczewska Katarzyna 
Published: September 2020

Currently, forensic research foundation is comprised of the methods of genetic analysis. The study of DNA polymorphism became a source of highly reliable evidence, which allow the determination of the genetic profile of biological traces containing genetic material of barely a few cells, collected from all possible substrates, and their further comparison with the genetic profile of the victim or suspect. The forensic expertise of such research, supported by relevant statistical calculations is one of the few objective evidence in criminal proceedings.The process of DNA testing for forensic purposes is composed of several stages and a number of analyzes. After securing suitable test specimen, the isolation of genetic material is performed. For the quantitative and qualitative analysis of the isolate, the Real Time PCR reaction is performed. This is a crucial moment for the study because it is the assessment of the suitability of samples for further testing. The next step is the amplification of DNA fragments with Multiplex PCR technique. Then, as a result of electrophoretic separation of the sequencer we obtain a genetic profile. Thus obtained profiling results are interpreted as well as compared by specialists.For analysts in the field of forensic medicine it is necessary to obtain clear genetic profiles. Given the often small amount of DNA that can be obtained and the need for unquestionability of the evidence, it is very important to develop a method with high sensitivity, which allows to obtain completely reliable results. In order to ensure the quality of the research, forensic laboratories must apply the standards and guidelines set by international associations, periodically calibrate their testing equipment, keep complete records of the results and, above all, to validate the used methods. In the laboratory, which intends to apply the procedure in question, internal validation must be carried out. The aim of this process is to determine the reliability and limitations of the method. During the test, the results of manufacturers’ verification are validated and the level of efficiency of the said procedure within a particular lab is checked.
Histone deacetylase inhibitors
Authors: Baran Marzena , Miziak Paulina Anna , Bonio Katarzyna 
Published: September 2020

The human genome is contained in chromatin, which is a complex macromolecular complex. It is made of DNA, histones and non-histone proteins. The structure of chromatin and the process of its rearrangement regulate the process of transcription, and hence gene expression. Deacetylase (HDAC) is a group of enzymes that catalyzes the cleavage of acetyl groups from lysine residues in histone and nonhistone proteins. This reaction is catalyzed by zinc or NAD + ions [3]. Histone deacetylases are present in the cytoplasm or nucleus of eukaryotes [4, 5]. These enzymes have been divided into 5 classes (I, IIa, IIb, III and IV) due to the similarity in structure and origin. Vorinostat is one of the most studied HDAC inhibitors. It belongs to the second generation polar-planar hydroxamic acid derivatives that inhibit class I and II histone deacetylases. Panobinostat and belinostat are HDAC inhibitors derived from hydroxamic acid that have also entered clinical trials. Valproic acid, from the group of aliphatic acids, belongs to inhibitors of class I and IIα deacetylases and is an established drug anticonvulsants. Histone deacetylase inhibitors may be useful in the treatment of neoplasms because they influence the action of factors related to cell proliferation, may cause cell cycle arrest, and coordinate the action of apoptotic factors and induce apoptosis. There are several deacetylase inhibitors available as drugs and are in different phases of clinical trials. They differ in potency and enzyme specificity. However, it is still unknown which deacetylases are essential for initiating and sustaining metabolic pathways leading to tumor development.
Pengaruh Pendidikan Buklet Kesehatan Terhadap Perilaku Ibu Hamil Terkait Upaya Pencegahan Berat Bayi Lahir Rendah (BBLR) Di Kota Semarang (Studi Kasus di Puskesmas Tlogosari wetan dan Puskesmas Genuk)
Authors: Azizah Luluk Faizatul , Nugrahaeni Sri Achadi , Hadi Cahyono 
Published: September 2020

Latar belakang dan tujuan: Angka kematian bayi akibat Berat Bayi Lahir Rendah (BBLR) di Kota Semarang masih tinggi. Dari 509 bayi BBLR dengan 36.6% mengalami kematian pada tahun 2017. Penelitian ini bertujuan untuk mengetahui pengaruh pendidikan kesehatan melalui buklet terhadap perilaku ibu hamil terkait upaya pencegahan BBLR di Kota Semarang. Metode: Penelitian eksperimen semu dengan desain pre post test with control group. Populasi dalam penelitian ini adalah semua ibu hamil di Kota Semarang pada Agustus – September tahun 2017. Subjek peneltian sejumlah 82 ibu hamil yang dipilih secara simple purposive sampling. Data dikumpulkan dengan wawancara menggunakan kuesioner terstruktur. Data dianalisis dengan Mann whitney.Hasil: Hasil penelitian menunjukan adanya peningkatan rerata skor pengetahuan pada kelompok intervensi dari 8,4 ± 2,1 (5-14) menjadi 13,4 ± 1,1 (11-15) dengan nilai p=0,001, sedangkan pada kelompok kontrol dari 7,3 ± 2,0 (3-11) menjadi 11,1 ± 1,3 (9-13) dengan nilai p=0,001. Peningkatan rerata skor sikap dari 37,5 ± 2,3 (28-41) menjadi 51,9 ± 3,2 (43-60) dengan nilai p=0,001, sedangkan pada kelompok kontrol dari 36,1 ± 2,2 (28-41) menjadi 37,2 ± 2,7 (28-43) dengan nilai p=0,001. Peningkatan rerata skor praktik dari 13,4 ± 1,9 (8-18) menjadi 18,1 ± 1,3 (13-20) dengan nilai p=0,001 sedangkan kelompok kontrol dari 14 ± 2,7 (7-18) menjadi 17,3 ±1,7 (12-19) dengan nilai p=0,018. Peningkatan skor pengetahuan (p<0,05), peningkatan sikap (p<0,05) dan praktik (p<0,05) pada kelompok intervensi lebih tinggi dibanding kelompok kontrol. Simpulan: Pendidikan buklet kesehatan yang dilaksanakan di Kota Semarang meningkatkan perilaku ibu hamil terkait upaya pencegahan BBLR. Diharapkan buklet kesehatan menjadi penambahan sarana pendidikan pada ibu hamil.
Faktor-Faktor yang Berhubungan dengan Implementasi Program Pengendalian Tuberkulosis di Puskesmas Wilayah Kabupaten Magelang
Authors: Lestari Ita Puji , Widagdo Laksmono , Adi Mateus Sakundarno 
Published: September 2020

Prevalensi TB di Provinsi Jawa Tengah pada tahun 2012 adalah sebesar 106,42 per 100.000 penduduk. Penemuan kasus dan Case Detection Ratedi bawah standar 70%, pada level kota/ kabupaten maupun level puskesmas dan untuk CDR terendah di Kabupaten Magelang yaitu 21,82%. Kabupaten Magelang pada tahun 2013 perkiraan kasus baru TB Paru BTA positif sebanyak 1285 orang dengan cakupan penemuan kasus TB Paru BTA positif pada tahun 2013 mencapai 17,98%. Penelitian ini bertujuan untuk mengetahui faktor-faktor yang berhubungan dengan implementasi program pengendalian TB di Puskesmas Kabupaten Magelang.Jenis penelitian adalah observasional analitik dengan pendekatan Cross Sectional. Responden dalam penelitian ini adalah seluruh petugas pelaksana yang terdiri satu perawat koordinator program, seorang tenaga laboratorium, dan serang dokter sebanyak 87 orang. Analisis data dilakukan secara multivariat.Hasil penelitian dengan uji statistik menunjukkan ada hubungan antara faktor komunikasi dengan implementasi (p=0,001), ada hubungan antara faktor disposisi dengan implementasi (p=0,001),ada hubungan antara faktor karakteristik badan pelaksana dengan implementasi (p=0,001), ada hubungan antara pemahaman standar dengan implementasi (p=0013),tidak ada hubungan antara faktor sumber daya dengan implementasi (p=0,240), dan tidak ada hubungan yang bermakna antara faktor lingkungan dengan implementasi program TB (p=0,057).Disarankan Puskesmas untuk menyusun instrumen yang mengukur efektifitas koordinasi dalam program,membuat kegiatan pendidikan dan pelatihan kaderisasi penyakit TB secara berkala. Puskesmas menjalin jejaring kerja sama dengan stakeholder dan masyarakat, menyusun pengembangan sistem reward bagi petugas maupun kader TB yang memiliki peran yang aktif ,menyusun suatu task force khusus untuk program pengendalian TB yang dilegalkan dengan Surat Keputusan dari Kepala Puskesmas.
Asupan Vitamin D yang Rendah, Obesitas dan Paparan Asap Rokok merupakan Faktor Risiko Preeklampsia Di Puskesmas Indramayu Tahun 2017
Authors: Nisa Roifatun , Kartasurya Martha Irene , Fatimah Siti 
Published: September 2020

Penyebab utama kematian ibu di Kabupaten Indramayu dari tahun 2012 - 2016 adalah preeklampsia yaitu 40 %. Penelitian ini bertujuan untuk menganalisis faktor-faktor risiko kejadian preeklampsia di Puskesmas Kabupaten Indramayu.Jenis penelitian observasional dengan rancangan kasus kontrol. Subyek sejumlah 55 kasus ibu preeklampsia dan 55 kasus ibu tidak preeklampsia dan dipilih secara purposive sampling. Pengumpulan data dilaksanakan dengan wawancara menggunakan kuesioner terstruktur, pengukuran antropometri dan metode food recall 2 x 24 jam. Analisis data dilakukan dengan chi-square dan regresi logistik ganda.Hasil penelitian menunjukkan faktor risiko terjadinya preeklampsia adalah umur kehamilan berisiko (<20 atau >35 tahun) (OR=5,4, p=0,001), riwayat preeklampsia sebelumnya (OR=7,1, p=0,001), riwayat preeklampsia dalam keluarga (OR=7,2, p=0,001), obesitas (OR=6,5, p=0,001), tingkat kecukupan protein kurang (OR=2,7, p=0,020), tingkat kecukupan vitamin D kurang (OR=3,7, p=0,013), stress (OR=2,6, p=0,013) dan paparan asap rokok (OR=2,3, p=0,030), secara multivariat umur kehamilan berisiko (<20 atau >35 tahun) (OR=2,9, p=0,047), riwayat preeklampsia (OR=4,3, p=0,024), riwayat preeklampsia dalam keluarga (OR=9,1, p=0,001), obesitas (OR=7,1, p=0,001) dan tingkat kecukupan protein (OR=4,1, p=0,026) secara bersama-sama merupakan faktor risiko kejadian preeklampsia. Disimpulkan bahwa faktor risiko yang paling kuat adalah riwayat preeklampsia dalam keluarga dan obesitas. Disarankan agar memasukkan riwayat preeklampsia dalam keluarga pada daftar data perawatan antenatal, mengintensifkan kunjungan nifas dan melakukan pengawasan bagi mereka yang telah terindentifikasi mempunyai risiko terjadinya preeklampsia.
Evaluasi Penerimaan Sistem Informasi Pelayanan Kesehatan Ibu Dengan Metode Tam Di Dinas Kesehatan Kabupaten Bungo
Authors: Martunus Martunus , Agushybana Farid , Nugraheni Sri Achadi 
Published: September 2020

Berdasarkan hasil studi pendahuluan didapatkan bahwa pengumpulan data kesehatan ibu pada dinas kesehatan Kabupaten Bungo sering mengalami keterlambatan pengumpulan, kurang lengkapnya pengisian data dan membutuhkan waktu yang lama untuk menyajikan data yang diperlukan. Salah satu model evaluasi yang dapat digunakan untuk menilai penerimaan dan penggunaan sebuah sistem teknologi informasi adalah evaluasi dengan menggunakan metode model penerimaan teknologi (Technology Acceptance Model atau TAM). Metode pada penelitian ini ialah oobservasional anallitik, menggunakan analisis regresi linear berganda untuk mengetahui hubungan antara variabel persepsi terhadap kemudahan, persepsi terhadap kemanfaatan dengan variabel sikap dan minat untuk menggunakan sistem informasi kesehatan ibu. Tujuan penelitian ini adalah Menerapkan evaluasi penerimaan sistem informasi pelayanan kesehatan ibu dengan menggunakan metode TAM di dinas kesehatan Kabupaten Bungo. Jenis penelitian yang digunakan adalah Kuantitatif. Subyek penelitian yaitu, bidan desa dan bidan koordinator di 19 puskesmas sejumlah 38 orang. Variabel persepsi terhadap kemudahan berpengaruh terhadap sikap untuk menggunakan SIK dengan nilai P-Value=0,000. Variabel persepsi terhadap kemudahan berpengaruh terhadap minat untuk menggunakan SIK dengan nilai P-Value=0,002. Variabel persepsi terhadap kemanfaatan berpengaruh terhadap sikap untuk menggunakan SIK dengan nilai P-Value=0,003. Variabel persepsi terhadap kemanfaatan berpengaruh terhadap minat untuk menggunakan SIK dengan nilai P-Value=0,002. Perlunya ada pelatihan yang berkelanjutan terkait Sistem Informasi Kesehatan Ibu sehingga dapat meningkatkan keterampilan dan menambah kepercayaan diri bidan dalam menggunakan Sistem Informasi Pelayanan Kesehatan Ibu.
Scanning rate enhancement in substrate integrated waveguide periodic leaky wave antenna with continuous beam scanning using delay lines
Authors: Chaudhary Dhruv , Agrawal Rahul , Gupta Suresh C. 
Published: September 2020

Abstract
In this paper, the scanning rate (SR) is enhanced for substrate integrated waveguide (SIW) based periodic leaky wave antenna (LWA) with continuous beam scanning. Delay line is inserted in the SIW based periodic LWA to modify the group delay profile which in turn increase the SR of the SIW based periodic LWA. Addition of the delay line enhances the SR of the SIW LWA to approximately three times from 15.6° to 47° per GHz. The prototype of the proposed LWA is fabricated and experimentally measured. The simulated and measured results show that the proposed LWA scans the angular range from −30° to +27° within a frequency span of only 1.2 GHz from 14.8 to 16 GHz (relative bandwidth of 7.7 %).