bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROP screening and treatment in four district-level special newborn care units in India: a cross-sectional study of screening and treatment rates
Authors: Sabherwal Shalinder , Gilbert Clare , Foster Allen , Kumar Praveen 
Published: March 2021

ObjectiveBlindness from retinopathy of prematurity (ROP) in middle-income countries is generally due to absence of screening or inadequate screening. The objective of this study was to assess uptake of services in an ROP programme in four district-level special newborn care units in India.DesignCross-sectional study.SettingAll four neonatal units of a state in India where model programme for ROP had been introducedPatientsInfants eligible for screening and treatment of ROP between March and May 2017.InterventionData on sex, birth weight and gestational age of eligible infants were collected and medical records reviewed for follow-up.Main outcome measuresProportion of eligible infants screened and for those screened, age at first screening, completion of screening, diagnosis and treatment received if indicated. The characteristics of infants screened and not screened were compared.Results137 (18%) of the 751 infants eligible for screening were screened at least once, with no statistically significant difference by sex. The mean birth weight and gestational age of those screened were significantly lower than those not screened. Among those screened, 43% underwent first screening later than recommended and 44% had incomplete follow-up. Fourteen infants (11% of those screened) were diagnosed with ROP. Five were advised laser treatment and all complied.ConclusionUptake, completion and timing of first screening was suboptimal. Some planned interventions including training of nursing staff, use of integrated data-management software and providing material for parent counselling, which have been initiated, need to be fully implemented to improve uptake of ROP screening services.
Smart agent system for insulin infusion protocol management: a simulation-based human factors evaluation study
Authors: Rosen Michael A , Romig Mark , Demko Zoe , Barasch Noah , Dwyer Cynthia , Pronovost Peter J , Sapirstein Adam 
Published: March 2021

ObjectiveTo compare the insulin infusion management of critically ill patients by nurses using either a common standard (ie, human completion of insulin infusion protocol steps) or smart agent (SA) system that integrates the electronic health record and infusion pump and automates insulin dose selection.DesignA within subjects design where participants completed 12 simulation scenarios, in 4 blocks of 3 scenarios each. Each block was performed with either the manual standard or the SA system. The initial starting condition was randomised to manual standard or SA and alternated thereafter.SettingA simulation-based human factors evaluation conducted at a large academic medical centre.SubjectsTwenty critical care nurses.InterventionsA systems engineering intervention, the SA, for insulin infusion management.MeasurementsThe primary study outcomes were error rates and task completion times. Secondary study outcomes were perceived workload, trust in automation and system usability, all measured with previously validated scales.Main resultsThe SA system produced significantly fewer dose errors compared with manual calculation (17% (n=20) vs 0, p<0.001). Participants were significantly faster, completing the protocol using the SA system (p<0.001). Overall ratings of workload for the SA system were significantly lower than with the manual system (p<0.001). For trust ratings, there was a significant interaction between time (first or second exposure) and the system used, such that after their second exposure to the two systems, participants had significantly more trust in the SA system. Participants rated the usability of the SA system significantly higher than the manual system (p<0.001).ConclusionsA systems engineering approach jointly optimised safety, efficiency and workload considerations.
Neoadjuvant chemoradiation alters biomarkers of anticancer immunotherapy responses in locally advanced rectal cancer
Authors: Seo Incheol , Lee Hye Won , Byun Sang Jun , Park Jee Young , Min Hyeonji , Lee Sung Hwan , Lee Ju-Seog , Kim Shin , Bae Sung Uk 
Published: March 2021

BackgroundNeoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.MethodsWe analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.ResultsGene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.ConclusionsTaken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.
CXCR6 deficiency impairs cancer vaccine efficacy and CD8+resident memory T-cell recruitment in head and neck and lung tumors
Authors: Karaki Soumaya , Blanc Charlotte , Tran Thi , Galy-Fauroux Isabelle , Mougel Alice , Dransart Estelle , Anson Marie , Tanchot Corinne , Paolini Lea , Gruel Nadege , Gibault Laure , Lepimpec-Barhes Francoise , Fabre Elizabeth , Benhamouda Nadine , Badoual Cecile , Damotte Diane , Donnadieu Emmanuel , Kobold Sebastian , Mami-Chouaib Fathia , Golub Rachel , Johannes Ludger , Tartour Eric 
Published: March 2021

BackgroundResident memory T lymphocytes (TRM) are located in tissues and play an important role in immunosurveillance against tumors. The presence of TRMprior to treatment or their induction is associated to the response to anti-Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1) immunotherapy and the efficacy of cancer vaccines. Previous work by our group and others has shown that the intranasal route of vaccination allows more efficient induction of these cells in head and neck and lung mucosa, resulting in better tumor protection. The mechanisms of in vivo migration of these cells remains largely unknown, apart from the fact that they express the chemokine receptor CXCR6.MethodsWe usedCXCR6-deficient mice and an intranasal tumor vaccination model targeting the Human Papillomavirus (HPV) E7 protein expressed by the TC-1 lung cancer epithelial cell line. The role of CXCR6 and its ligand, CXCL16, was analyzed using multiparametric cytometric techniques and Luminex assays.Human biopsies obtained from patients with lung cancer were also included in this study.ResultsWe showed that CXCR6 was preferentially expressed by CD8+TRMafter vaccination in mice and also on intratumoral CD8+TRMderived from human lung cancer. We also demonstrate that vaccination of Cxcr6-deficient mice induces a defect in the lung recruitment of antigen-specific CD8+T cells, preferentially in the TRMsubsets. In addition, we found that intranasal vaccination with a cancer vaccine is less effective in theseCxcr6-deficient mice compared with wild-type mice, and this loss of efficacy is associated with decreased recruitment of local antitumor CD8+TRM. Interestingly, intranasal, but not intramuscular vaccination induced higher and more sustained concentrations of CXCL16, compared with other chemokines, in the bronchoalveolar lavage fluid and pulmonary parenchyma.ConclusionsThis work demonstrates the in vivo role of CXCR6-CXCL16 axis in the migration of CD8+resident memory T cells in lung mucosa after vaccination, resulting in the control of tumor growth. This work reinforces and explains why the intranasal route of vaccination is the most appropriate strategy for inducing these cells in the head and neck and pulmonary mucosa, which remains a major objective to overcome resistance to anti-PD-1/PD-L1, especially in cold tumors.
Cross sections for 2-to-1 meson–meson scattering
Authors: Li Wan-Xia , Xu Xiao-Ming , Weber H. J. 
Published: March 2021

AbstractWe study the processes $$K{\bar{K}} \rightarrow \phi $$

K

K

¯

→
ϕ

, $$\pi D \rightarrow D^*$$

π
D
→

D
∗

, $$\pi {\bar{D}} \rightarrow {\bar{D}}^*$$

π

D

¯

→

D

¯

∗

, and the production of $$\psi (3770)$$

ψ
(
3770
)

, $$\psi (4040)$$

ψ
(
4040
)

, $$\psi (4160)$$

ψ
(
4160
)

, and $$\psi (4415)$$

ψ
(
4415
)

mesons in collisions of charmed mesons or charmed strange mesons. The process of 2-to-1 meson–meson scattering involves a quark and an antiquark from the two initial mesons annihilating into a gluon and subsequently the gluon being absorbed by the spectator quark or antiquark. Transition amplitudes for the scattering process derive from the transition potential in conjunction with mesonic quark–antiquark wave functions and the relative-motion wave function of the two initial mesons. We derive these transition amplitudes in the partial wave expansion of the relative-motion wave function of the two initial mesons so that parity and total-angular-momentum conservation are maintained. We calculate flavor and spin matrix elements in accordance with the transition potential and unpolarized cross sections for the reactions using the transition amplitudes. Cross sections for the production of $$\psi (4040)$$

ψ
(
4040
)

, $$\psi (4160)$$

ψ
(
4160
)

, and $$\psi (4415)$$

ψ
(
4415
)

relate to nodes in their radial wave functions. We suggest the production of $$\psi (4040)$$

ψ
(
4040
)

, $$\psi (4160)$$

ψ
(
4160
)

, and $$\psi (4415)$$

ψ
(
4415
)

as probes of hadronic matter that results from the quark–gluon plasma created in ultrarelativistic heavy-ion collisions.
A bi-directional approach to comparing the modular structure of networks
Authors: Straulino Daniel , Landman Mattie , O’Clery Neave 
Published: March 2021

AbstractHere we propose a new method to compare the modular structure of a pair of node-aligned networks. The majority of current methods, such as normalized mutual information, compare two node partitions derived from a community detection algorithm yet ignore the respective underlying network topologies. Addressing this gap, our method deploys a community detection quality function to assess the fit of each node partition with respect to the other network’s connectivity structure. Specifically, for two networks A and B, we project the node partition of B onto the connectivity structure of A. By evaluating the fit of B’s partition relative to A’s own partition on network A (using a standard quality function), we quantify how well network A describes the modular structure of B. Repeating this in the other direction, we obtain a two-dimensional distance measure, the bi-directional (BiDir) distance. The advantages of our methodology are three-fold. First, it is adaptable to a wide class of community detection algorithms that seek to optimize an objective function. Second, it takes into account the network structure, specifically the strength of the connections within and between communities, and can thus capture differences between networks with similar partitions but where one of them might have a more defined or robust community structure. Third, it can also identify cases in which dissimilar optimal partitions hide the fact that the underlying community structure of both networks is relatively similar. We illustrate our method for a variety of community detection algorithms, including multi-resolution approaches, and a range of both simulated and real world networks.
A Note on Cube-Full Numbers in Arithmetic Progression
Authors: Zhong Mingxuan , Ma Yuankui 
Published: March 2021

We obtain an asymptotic formula for the cube-full numbers in an arithmetic progression

n
≡
l

mod

q

, where

q
,
l

=
1

. By extending the construction derived from Dirichlet’s hyperbola method and relying on Kloosterman-type exponential sum method, we improve the very recent error term with

x

118

/

4029

<
q

.
Dynamic Changes of Post-Radiotherapy Plasma Epstein–Barr Virus DNA in a Randomized Trial of Adjuvant Chemotherapy Versus Observation in Nasopharyngeal Cancer
Authors: Hui Edwin Pun , Ma Brigette B.Y. , Lam W.K. Jacky , Chan K.C. Allen , Mo Frankie , Ai Qi-yong Hemis , King Ann D. , Wong Chi Hang , Wong Kenneth C.W. , Lam Daisy C.M. , Tong Macy , Poon Darren M.C. , Li Leung , Lau Thomas K.H. , Wong Kwan Hung , Lo Y.M. Dennis , Chan Anthony T.C. 
Published: March 2021

Abstract

Purpose:
To study the dynamic changes in plasma Epstein–Barr virus (pEBV) DNA after radiotherapy in nasopharyngeal cancer (NPC).

Experimental Design:
We conducted a randomized controlled trial of adjuvant chemotherapy versus observation in patients with NPC who had detectable pEBV DNA at 6 weeks post-radiotherapy. Randomized patients had a second pEBV DNA checked at 6 months post-randomization. The primary endpoint was progression-free survival (PFS).

Results:
We prospectively enrolled 789 patients. Baseline post-radiotherapy pEBV DNA was undetectable in 573 (72.6%) patients, and detectable in 216 (27.4%) patients, of whom 104 (13.2%) patients were eligible for randomization to adjuvant chemotherapy (n = 52) versus observation (n = 52). The first post-radiotherapy pEBV DNA had a sensitivity of 0.48, specificity of 0.81, area under receiver-operator characteristics curve (AUC) of 0.65, false positive (FP) rate of 13.8%, and false negative (FN) rate of 14.4% for disease progression. The second post-radiotherapy pEBV DNA had improved sensitivity of 0.81, specificity of 0.75, AUC of 0.78, FP rate of 14.3%, and FN rate of 8.1%. Patients with complete clearance of post-radiotherapy pEBV DNA (51%) had survival superior to that of patients without post-radiotherapy pEBV DNA clearance (5-year PFS, 85.5% vs. 23.3%; HR, 9.6; P &lt; 0.0001), comparable with patients with initially undetectable post-radiotherapy pEBV DNA (5-year PFS, 77.1%), irrespective of adjuvant chemotherapy or observation.

Conclusions:
Patients with NPC with detectable post-radiotherapy pEBV DNA who experienced subsequent pEBV DNA clearance had superior survival comparable with patients with initially undetectable post-radiotherapy pEBV DNA. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC.
Antidrug Antibodies and Drug Development: Challenges in the Immunotherapy Era
Authors: de Spéville Bernard Doger , Moreno Victor 
Published: March 2021

Abstract
Novel antibody formats such as bispecifics have increased risk of immunogenicity, impacting safety and efficacy. LY3415244, a novel T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM3)-PDL1 (programmed death (ligand) 1) bispecific caused neutralizing antibody–drug antibodies (ADA) in 12 of 12 patients and required study termination. Novel approaches are needed to ameliorate and manage this undesirable effect of therapeutic antibodies.
See related article by Hellmann et al., p. 2773
НЕОНАТАЛЬНИЙ СКРИНІНГ НА ТЯЖКІ КОМБІНОВАНІ ІМУНОДЕФІЦИТИ: РЕТРОСПЕКТИВА І СУЧАСНІСТЬ
Authors: Yarema Н. M. , Boyarchuk O. R. , Mochulska O. M. 
Published: March 2021

Мета роботи – аналіз даних наукових публікацій, які висвітлюють зарубіжний досвід імплементації тяжких комбінованих імунодефіцитів у неонатальний скринінг.
Матеріали та методи. Проаналізовані публікації з баз даних Web of Science, Scopus і PubMed, що описують клінічну й економічну ефективність скринінгу на тяжкі комбіновані імунодефіцити.
Тяжкі комбіновані імунодефіцити відносять до найтяжчих станів серед первинних імунодефіцитів. Немовлята із тяжким комбінованим імунодефіцитом схильні до небезпечних для життя інфекцій. Без ранньої діагностики й ефективного лікування їх смертність значно зростає, що зумовлює медико-соціальну значущість цих захворювань. У багатьох країнах впроваджено обстеження новонароджених на тяжкі комбіновані імунодефіцити методом ПЛР для аналізу TREC/KREC.
Результати дослідження та їх обговорення. За даними літератури, практичний досвід впровадження у практику неонатального скринінгу на тяжкі комбіновані імунодефіцити у зарубіжних країнах показує, що таке тестування є чутливе і специфічне, має відносно низьку вартість, легко виявляє дітей із безсимптомним перебігом. Зазначені можливості дозволяють швидко виявити порушення клітинного імунітету, ідентифікувати тяжкі комбіновані імунодефіцити, розпочати адекватне лікування пацієнтів, проводити заходи для попередження розвитку інфекцій та рятувати життя.
Висновки. Тяжкі комбіновані імунодефіцити відповідають критеріям включення нозології в систему широкомасштабного неонатального скринінгу, а зарубіжний досвід впровадження в практику неонатального скринінгу може бути корисним для України. Cкринінг на тяжкі комбіновані імунодефіцити новонароджених можна імплементувати у клінічну практику в Україні.
ВПЛИВ ХІРУРГІЧНОЇ СТИМУЛЯЦІЇ ОВУЛЯЦІЇ ШЛЯХОМ ФЕРТИЛОСКОПІЧНОГО ОВАРІАЛЬНОГО ДРИЛІНГУ НА ГОРМОНАЛЬНИЙ СТАТУС ПАЦІЄНТОК ІЗ КЛОМІФЕН-РЕЗИСТЕНТНОЮ ФОРМОЮ СИНДРОМУ ПОЛІКІСТОЗНИХ ЯЄЧНИКІВ ТА ОЖИРІННЯМ
Authors: Chaika V. V. 
Published: March 2021

Мета дослідження – вивчити вплив хірургічної стимуляції овуляції шляхом фертилоскопічного оваріального дрилінгу на гормональний статус пацієнток із кломіфен-резистентною формою синдрому полікістозних яєчників (СПКЯ) та ожирінням.
Матеріали та методи. Під спостереженням перебувала 61 жінка репродуктивного віку. В основну групу ввійшла 31 жінка із кломіфен-резистентним СПКЯ і з індексом маси тіла >30 кг/м2, яким хірургічну стимуляцію овуляції виконано з використанням ТВГЛ у Київському міському центрі репродуктивної та перинатальної медицини за період 2017–2019 рр. У контрольну групу увійшли 30 умовно соматично і гінекологічно здорових жінок. Пацієнтки пройшли комплексне обстеження. Концентрації гонадотропінів, статевих стероїдів та антимюллерового гормону в сироватці периферичної крові досліджували імунохімічним методом на 2–3-й день менструального циклу перед операцією, через 1, 3 і 6 місяців після операції.
Результати дослідження та їх обговорення. Після проведення хірургічної стимуляції відмічали поліпшення гормонального профілю сироватки периферичної крові зі зниженням лютеїнізуючого гормону, статевих стероїдів та підвищенням фолікулостимулюючого гормону, але через 3 місяці спостерігали тенденцію до поступового повернення вмісту гонадотропінів та статевих стероїдів до вихідного передопераційного рівня. Через 6 місяців після хірургічної стимуляції овуляції найбільш стійкими залишалися зниження порівняно з контрольними значеннями сироваткової концентрації антимюллерового гормону в 1,24 (р<0,01), вільного тестостерону – в 1,61 (р<0,01) і дегідроепіандростерону – в 1,69 раза (р<0,01). Поліпшення гормонального статусу безпосередньо після хірургічної стимуляції овуляції привело до настання у прооперованих пацієнток вагітності впродовж 3 місяців у 26,81 % випадків, впродовж 6 місяців – у 35,48 %.
Висновок. Отримані дані вказують на те, що перші 6 місяців після хірургічної стимуляції овуляції є найбільш перспективними для планування і настання вагітності у кломіфен-резистентних пацієнток із СПКЯ і ожирінням.
EXPRESSION OF MARKERS OF HYPOXIA, ANGIOGENESIS, AS MICROCIRCULATORY-TISSUE FACTORS IN PROLIFERATIVE PROCESSES OF THE ENDOMETRIUM
Authors: Chumak Z. V. , Shapoval M. V. , Nadvorna О. М. , Zhovtenko O. V. 
Published: March 2021

The aim of the study – to learn the expression of VEGF and HIF-1α in physiological, hyperplastic, atypical endometrium at different ages of women.
Materials and Methods. Evaluation of VEGF expression and HIF-1α performed in endometrial tissue samples in 458 women of late reproductive, perimenopausal and postmenopausal age. Expression of VEGF and HIF-1α was performed at the mRNA level by polymerase chain reaction of cDNA obtained by reverse transcription. The results were processed by the method of variation statistics with the assessment of reliability according to the Student's criterion using standard computer systems.
Results and Discussion. Analyzing the data of the presented work, higher VEGF expression rates were found in atypical hyperplasia in all age categories, but probably higher rates were found in the postmenopausal period, in atypical endometrial hyperplasia, which indicates the need for vigilance in detecting this process in the appropriate age category. Studies have shown that HIF-1α can potentiate the activation of vasomotor genes that are required for the vascular response to hypoxia. These studies demonstrate the informativeness of the method of determining HIF-1α in the examination of patients with endometrial hyperplastic processes (EHP). The introduction of this method in practical medicine will not only understand the details of the changes occurring in the body (pathological, physiological), but also develop strategic maneuvers for possible therapeutic or surgical treatments.
Conclusions. Expression of VEGF and HIF-1α levels in endometrial tissue cells as a marker can be a promising method for diagnosing the risk of proliferative conditions and their prognosis, especially in combination with other markers that characterize immunohistochemical and molecular genetic cellular parameters. Hypoxia and its relationship with indicators of angiogenesis may have some promising significance. Because the development of pathological conditions develops at a certain stage of hypoxic conditions. Under certain conditions, as a result of disruption of tissue processes, possibly metabolic, changes in angiogenesis are reduced with increasing hypoxia, which may in the long run provoke atypical disorders.