bluuebunny/crossref_metadata_2025 huggingface dataset:
Seletividade alimentar e o papel da escola: crianças que frequentam regularmente a escola apresentam maior repertório alimentar?
Authors: Braga Mariana Correia Stevenson , Nogueira Luana Romão , Okuizumi Arissa Matsuyama , Rocha Nilvane Oliveira , Almeida Andrea Romero de , Maximino Priscila , Fisberg Mauro
Published: December 2021

Objetivo: Comparar o número de alimentos aceitos por crianças de 0 a 5 anos com seletividade alimentar que frequentam ou não a escola. Métodos: Estudo observacional retrospectivo, com dados de 94 crianças de 0 a 5 anos diagnosticadas com seletividade alimentar atendidas em um centro de referência. O diagnóstico do paciente é baseado na classificação de Kerzner e o repertório alimentar foi avaliado por meio do inventário alimentar. A frequência da criança à escola ou não foi autorreferida pelo responsável da criança. Para os testes de diferenças utilizou-se o qui-quadrado e o T de student, dependendo da natureza da variável. Para todas as análises, considerou-se nível de significância menor que 5%. Resultados: No presente estudo, a maioria das crianças era do sexo masculino (64,9%), com mais de 2 anos (78,7%), eutrófica de acordo com IMC para idade (86,0%), seletivo regular (77,7%) e sem doença orgânica associada (63,7%). O número médio de alimentos aceitos pela amostra foi de 19,2±7,7 alimentos. Em relação a frequentar a escola ou não, 67,0% frequenta a escola regularmente. Apesar de haver valor médio menor de alimentos quando não se frequenta a escola (17,8±7,3 vs 20,8±7,8, quando frequenta), não houve diferença estatisticamente significativa (p=0,074). De modo geral, foram encontradas médias maiores quando há a frequência na escola. Crianças com risco de sobrepeso/sobrepesas ou que foram amamentadas exclusivamente até os 6 meses e que frequentam a escola apresentam maior média de alimentos aceitos quando comparadas às que não frequentam (p=0,002 e p=0,046, respectivamente). Conclusão: Crianças altamente seletivas vão menos à escola do que os seletivos regulares. Crianças com risco de sobrepeso e sobrepesas que não frequentam a escola apresentam seletividade mais severa.
Nevo epidérmico verrucoso inflamatório linear e diagnóstico diferencial com a psoríase linear
Authors: Zemero Maria Isabel Muniz , Santos Maria Amélia Lopes dos , Mendes Alena Margareth Darwich , Pires Carla Andrea Avelar
Published: December 2021

O nevo epidérmico verrucoso inflamatório linear (NEVIL) é uma variedade clínica rara de nevo epidérmico verrucoso, que se manifesta no início da infância, como lesões inflamatórias de superfície ceratósica, que coalescem e se distribuem em faixa, acompanhando as linhas de Blaschko. Faz diagnóstico diferencial com a psoríase linear, sendo difícil a diferenciação, dado os aspectos clínicos e histopatológicos comuns aos dois, enfantizando-se a necessidade de conhecer as características específicas de cada um. O objetivo deste relato é demonstrar uma afecção relativamente rara, descrita em uma  menina de 5 anos, evoluindo desde os primeiros dias de vida com placas papuloceratósicas dispostas linearmente, acompanhadas de sinais inflamatórios e áreas erosadas ocupando grandes lábios, períneo e face interna e superior da coxa esquerda. Também pápulas e placas ceratósicas na região cervical posterior e borda lateral externa da planta do pé esquerdo, ascendendo ao longo da região posterior deste membro. Os critérios clínicos e histopatológicos corroboram o diagnóstico de NEVIL na diferenciação com a psoríase linear, ressaltando a importância do estabelecimento de critérios/ ferramentas que auxiliem na diferenciação destas duas dermatoses visando agilizar o diagnóstico, otimizar o tratamento e minimizar o desconforto para esses pacientes. O acompanhamento a longo prazo dos portadores é sugerido pela possibilidade ainda que mínima de malignização do NEVIL.
Perfil clínico e terapêutico dos pacientes com hipertireoidismo do ambulatório de endocrinologia de um hospital universitário do sul do Brasil
Authors: Parabocz Rafael Antonio , Carvalho Renata Soares , Schrut Gianna Carla Alberti , Kluthcovsky Ana Claudia Garabeli Cavalli , Stumpf Matheo Augusto Morandi
Published: December 2021

Introdução: O hipertireoidismo decorre da elevação sérica dos hormônios tireoidianos, secundário a hiperfunção da glândula tireoide. As causas mais prevalentes são a Doença de Graves (DG) e os Bócios Nodulares Tóxicos (BNT). As principais formas de tratamento são as drogas anti-tireoideanas (DAT), ablação com iodo radioativo (DTI131) e a tireoidectomia. Métodos: Estudo transversal, descritivo, com inclusão de pacientes com diagnóstico de hipertireoidismo por DG e BNT; foram coletados dados epidemiológicos, clínicos, laboratoriais e de tratamento. Resultados: A maioria dos pacientes foi referenciada pela atenção primária e encontrava-se em uso prévio de DAT. A variável idade obteve diferença estatisticamente significativa entre as etiologias de DG e BNT, e em ambas, houve predomínio de incidência no sexo feminino. A DG apresentou maior frequência de sinais e sintomas de tireotoxicose, ao passo que o BNT mostrou mais sinais e sintomas de compressão. Houve remissão da doença em 23,2% dos pacientes com DG. Em 23,2% dos pacientes optou-se pela manutenção de metimazol em baixa dose por mais de 36 meses e em 16,1% foi realizado tratamento definitivo. No BNT foram preferidas terapias definitivas, principalmente a tireoidectomia em 27,5% dos pacientes. Doses baixas de metimazol por mais de 36 meses foram utilizados também no BNT, em 22,5% dos pacientes. Conclusão: O hipertireoidismo é uma doença heterogênea, desde a clínica inicial até a terapêutica, entre suas etiologias mais prevalentes. Observou-se uma tendência de priorizar as terapias medicamentosas em longo prazo com baixas doses tanto na DG, quanto no BNT.
Razvoj sestrinstva u Karlovcu u razdoblju od osnutka grada do prve polovice 20. stoljeća
Authors: Mirilović Snježana , Pavlić Blaženka , Vižintin Karolina , Gavrilidis Afrodita
Published: December 2021

Uvod: Povijest skrbi za bolesne i potrebite u Karlovcu veže se za osnutak grada. Bolnice se grade isprva unutar tvrđave, a od 1779. godine i izvan tvrđave. Osoblje koje je radilo u bolnicama bili su priučeni liječnici koji su se s vremenom stručno osposobljavali. Njihova se imena navode u najranijim bolničkim spisima. Rad osoba koje su pomagale liječnicima i njegovale bolesnike oskudno je opisan i ne nalazimo podatke o tome tko su bile prve školovane medicinske sestre koje su radile u Karlovcu. Autorice su u radu pokušale učiniti rekonstrukciju početaka sestrinstva u Karlovcu i pronaći imena prvih sestara te podatke o školovanju i djelokrugu i/ili mjestu rada. Metode: Polazište za izradu rada bili su dokumenti pohranjeni u pismohrani Opće bolnice Karlovac, arhivskim fondovima i zbirkama Hrvatskog državnog arhiva (HDA) te Državnom arhivu u Karlovcu (DAKA), kao i dokumenti pohranjeni u pismohrani Škole za medicinske sestre Mlinarska, Družbe sestara milosrdnica sv. Vinka Paulskog u Zagrebu, i Milosrdnih sestara sv. Križa u Đakovu. Kao dopuna ovim izvorima korišteni su do sada objavljeni radovi. Rezultati: Pregledom pronađene povijesne građe saznajemo da se do 19. stoljeća ne nalaze imena ni zvanja osoba koje su njegovale bolesne. Postoje zapisi o imenima i prezimenima liječnika i bolesnika, ali za pomoćno se osoblje pretpostavlja da su to bile priučene žene. Kao prvi educirani kadar spominju se redovnice koje su krajem 19. stoljeća došle raditi u gradsku javnu bolnicu. Redovnice su radile i u sklopu Crvenog križa te priručnim bolnicama zajedno s građankama Karlovca. Na temelju uvida u arhivsku građu doznaju se imena sestara koje su djelovale u Karlovcu, kao i njihov djelokrug te mjesto rada. Osobe koje se najranije spominju u zapisima su primalje Ana Lamprecht i Sofija Piljuga, ali nisu pronađeni podaci o njihovoj izobrazbi. Na temelju pregledane povijesne građe može se izdvojiti Perpetua Kovačić koja je bila zaposlena u Karlovcu kao prva redovnica koja se školovala u Školi za sestre pomoćnice u Zagrebu. Zaključak: Cjelokupan sestrinski rad u bolnicama u Karlovcu provodile su većinom redovnice. Brinule su o bolesnima, pripremale hranu, uređivale okoliš i provodile higijenu u bolnici. Rad je bio zahtjevan i popraćen teškim radnim uvjetima. Analizom povijesne građe doznaju se mnoga imena osoba koje su njegovale i skrbile o bolesnima u Karlovcu. Daljnjim istraživanjem i analizom povijesnog materijala moglo bi se doći do dodatnih i/ili novih informacija te drugačijih zaključaka. Ostaje nepoznat podatak o osobama koje su njegovale bolesnike u gradskoj javnoj bolnici u razdoblju od njezina osnutka do dolaska prvih redovnica.
Povijesni osvrt na rad Marije Brozović (1914.-1987.)
Authors: Križić Marija
Published: December 2021

Uvod: Skrb za bolesne u Koprivnici u svojim je začecima usko povezana s radom redovnica iz Družbe sestara milosrdnica sv. Vinka Paulskog. Prve školovane medicinske sestre na područje Koprivnice dolaze nakon otvaranja Školske poliklinike 1928. godine. Tako su u razdoblju od 1928. do 1937. godine u Koprivnici radile, uglavnom kraće vrijeme, Zlata Baldić, Štefanija Holjevac, Sofija Pavleković Stipetić i Marija Pavlović. Marija Brozović u Koprivnicu dolazi 1937. godine. Pregledom pronađene dokumentacije željelo se dobiti uvid u rad i doprinos Marije Brozović u razvoju sestrinske profesije na području grada Koprivnice. Metode: Rekonstrukcija podataka temeljila se na fondovima i zbirkama Hrvatskog državnog arhiva (HDA), objavljenim člancima u Glasu Podravine, usmenom svjedočanstvu obitelji Marije Brozović i dokumentima sačuvanima u privatnom posjedu. Kao dopuna navedenim izvorima korišteni su publicirani radovi na obrađenu temu. Rezultati: Marija Brozović rođena je 13. rujna 1914. godine u Sloveniji, gdje je završila osnovnu školu i gimnaziju.Školu za sestre pomoćnice u Zagrebu upisuje 1934. Diplomirala je 1936. godine. Nakon završetka školovanja, počinje raditi u Crvenom križu Banovine savske u Zagrebu, a godinu dana kasnije dolazi u Školsku polikliniku grada Koprivnice. Godine 1945. prelazi raditi u Dom narodnog zdravlja gdje radi do 1958. kada postaje glavnom sestrom Zdravstvenog centra i ravnateljicom Škole za bolničare. Dužnost glavne sestre obnaša do 1962. godine nakon čega radi u Antituberkuloškom dispanzeru do umirovljenja 1972. godine. Umrla je 28. listopada 1987. u Koprivnici. Zaključak: Iako Marija Brozović nije prva medicinska sestra koja je došla raditi u Koprivnicu, razvidan je njezin velik doprinos u razvoju preventivne medicinske djelatnosti i sestrinstva na području Koprivnice. Prepoznala je nedostatak stručnog osoblja u bolnici te bila jedan od inicijatora osnivanja Škole za bolničare s mišlju što bržeg osiguravanja školovanog osoblja kao preduvjeta pružanja kvalitetnije skrbi za bolesnike. Prepoznala je potrebe i probleme organizacije sestrinske službe na području Koprivnice. Bila je svjesna potencijala medicinskih sestara te je vizionarski svojim aktivnostima i primjerom razvijala sestrinstvo na području Koprivnice cijeli radni vijek.
Smiljana (Smiljka) Nell, (Zagreb, 23. listopada 1931. – Zagreb, 28. srpnja 2021.) – Širina interesa i predanost u službi sestrinstva
Authors: Kičin Ercegovac Gordana
Published: December 2021

Smiljana (Smiljka) Nell rođena je 23. listopada 1931. godine u Zagrebu kao jedino dijete obitelji Nell. Osnovnu školu završila je u Zagrebu te je nakon položene male mature upisala gimnaziju. Uz gimnaziju završila je i srednju glazbenu školu. Po završetku gimnazije upisala se u Školu za medicinske sestre u Mlinarskoj ulici u Zagrebu, gdje je diplomirala 1950. godine. Nakon diplome počinje raditi u Klinici za infektivne bolesti „Dr. Fran Mihaljević“ u Zagrebu. Dvije godine kasnije upisala je poslijediplomski studij za medicinske sestre u Školi narodnog zdravlja u Zagrebu i diplomirala sestrinstvo u javnom zdravstvu. Pravni fakultet Sveučilišta u Zagrebu upisala je 1977. godine kao izvanredni student te je odslušala predmete s prve godine. Od 1968. do 1988. godine (do odlaska u mirovinu) bila je g lavna sestra Klinike za infektivne bolesti „Dr. Fran Mihaljević“. Smiljka Nell bila je inicijator osnivanja i prva predsjednica Sekcije sestara infektoloških odjela Socijalističke Republike Hrvatske (danas Hrvatska udruga medicinskih sestara, Infektološko društvo). Sekcija je osnovana u Zagrebu 1969. godine, a Smiljka Nell obavljala je dužnost predsjednice od 1969. do 1973. godine nakon čega obnaša dužnost tajnice Društva medicinskih sestara i tehničara SR Hrvatske, do 1975. godine. U njezinu mandatu održana su prva tri Savjetovanja sestara infektoloških odjela i klinika Socijalističke Republike Hrvatske. Bila je član uređivačkog odbora Vjesnika medicinskih sestara i medicinskih tehničara SR Hrvatske od 1970. do kraja 1973. godine. Smiljka Nell učinila je velik iskorak u unapređenju sestrinstva, a posebice organizacije rada infektoloških odjela cijele Hrvatske te je sve do odlaska u mirovinu, krajem 1988. godine, zbog svih svojih aktivnosti smatrana vrlo utjecajnom medicinskom sestrom u području skrbi za infektološke bolesnike. Preminula je 28. srpnja 2021. godine.
ÖRGÜTSEL SİNİZM ÜZERİNDE DÖNÜŞÜMCÜ VE ETKİLEŞİMCİ LİDERLİK TARZLARININ ETKİSİ
Authors: POLATCI Sema , MÜLAYİM Merve
Published: December 2021

Örgütsel sinizm, çalışanların örgütleri ile ilgili olumsuz tutumlarını ifade etmektedir. Örgütlerde sinizmi engellemede liderlik kavramı büyük önem taşımaktadır. Bu sebeple, örgütlerin değişim ve yenilenme süreçlerinde, dönüşümcü ve etkileşimci liderlik davranışları ele alınarak örgütsel sinizme yönelik etkilerinin değerlendirilmesi amaçlanmıştır. Çalışmada, Elazığ ili bankacılık sektöründe faaliyet gösteren banka çalışanlardan kolayda örnekleme yöntemi ile veri toplanmıştır. Araştırma sonucunda dönüşümcü ve etkileşimci liderlik tarzlarının her ikisinin de örgütsel sinizmi negatif yönde etkiledikleri tespit edilmiştir. Araştırma sonuçlarından en önemlisi ise örgütsel sinizm üzerinde dönüşümcü liderlik tarzının etkileşimci liderlik tarzından daha etkili olmasıdır. Etkileşimci liderlik tarzı sadece duygusal sinizmi azaltırken, dönüşümcü liderlik tarzının örgütsel sinizmin tüm alt boyutlarında negatif etkiye sahip olduğu ortaya konulmuştur. Elde edilen bulgular ışığında örgütsel sinizm ile ilgili çözüm önerileri geliştirilmeye çalışılmıştır.
TÜRKİYE’DE DÖVİZ KURUNUN TEMEL DİNAMİKLERİ
Authors: GÜVENOĞLU Hüseyin , KARAHAN Özcan
Published: December 2021

Döviz kuru ekonomide çok sayıda makroekonomik göstergeyi yakından etkileyen önemli bir faktördür. Öyle ki, döviz kurundaki dalgalanmalar ekonomik faaliyetleri olumsuz yönde etkileyerek ciddi krizlere yol açabilmektedir. Bu nedenle döviz kuru politikalarının başarılı bir biçimde uygulanması ekonomik istikrarın sağlanmasında çok büyük bir rol oynamaktadır. Döviz kuru politikalarının başarılı bir biçimde uygulanması ise her şeyden önce söz konusu politikaların etkin bir biçimde tasarlanmasını gerektirmektedir. Döviz kuru politikasının etkin bir biçimde tasarlanması ise döviz kuru seviyesini etkileyen dinamiklerin kapsamlı bir biçimde tespit edilmesine bağlıdır. Buradan hareketle çalışmada 2009:Q1–2019:Q4 dönemine ait üçer aylık veriler kullanılarak Türkiye’de döviz kurunu belirleyen temel dinamikler analiz edilmiştir. Bunun için döviz piyasasındaki arz ve talep koşullarını doğrudan doğruya etkileyen faktörler olan finansal sermaye hareketleri ile net ihracatın döviz kuru üzerindeki etkisi ARDL modeli kullanılarak incelenmiştir. Ekonometrik sonuçlar finansal sermaye hareketlerinin döviz piyasasındaki arz ve talep koşulları üzerinde net ihracata göre daha etkili olduğunu göstermiştir. Buna göre finansal sermaye hareketlerinin döviz kuru üzerindeki etkisi kısa ve uzun dönemde net ihracata göre daha baskın bulunmuştur. Böylece, döviz kuru seviyesinde istikrar sağlamayı hedefleyen politikaların uygulanması sürecinde Türkiye'ye yönelik sermaye hareketlerinin etkin bir biçimde yönetilmesine daha çok ağırlık verilmelidir.
Behavioral Prioritization Enhances Working Memory Precision and Neural Population Gain
Authors: Yoo Aspen H. , Bolaños Alfredo , Hallenbeck Grace E. , Rahmati Masih , Sprague Thomas C. , Curtis Clayton E.
Published: December 2021

Humans allocate visual working memory (WM) resource according to behavioral relevance, resulting in more precise memories for more important items. Theoretically, items may be maintained by feature-tuned neural populations, where the relative gain of the populations encoding each item determines precision. To test this hypothesis, we compared the amplitudes of delay period activity in the different parts of retinotopic maps representing each of several WM items, predicting the amplitudes would track behavioral priority. Using fMRI, we scanned participants while they remembered the location of multiple items over a WM delay and then reported the location of one probed item using a memory-guided saccade. Importantly, items were not equally probable to be probed (0.6, 0.3, 0.1, 0.0), which was indicated with a precue. We analyzed fMRI activity in 10 visual field maps in occipital, parietal, and frontal cortex known to be important for visual WM. In early visual cortex, but not association cortex, the amplitude of BOLD activation within voxels corresponding to the retinotopic location of visual WM items increased with the priority of the item. Interestingly, these results were contrasted with a common finding that higher-level brain regions had greater delay period activity, demonstrating a dissociation between the absolute amount of activity in a brain area and the activity of different spatially selective populations within it. These results suggest that the distribution of WM resources according to priority sculpts the relative gains of neural populations that encode items, offering a neural mechanism for how prioritization impacts memory precision.
How Working Memory and Reinforcement Learning Are Intertwined: A Cognitive, Neural, and Computational Perspective
Authors: Yoo Aspen H. , Collins Anne G. E.
Published: December 2021

Reinforcement learning and working memory are two core processes of human cognition and are often considered cognitively, neuroscientifically, and algorithmically distinct. Here, we show that the brain networks that support them actually overlap significantly and that they are less distinct cognitive processes than often assumed. We review literature demonstrating the benefits of considering each process to explain properties of the other and highlight recent work investigating their more complex interactions. We discuss how future research in both computational and cognitive sciences can benefit from one another, suggesting that a key missing piece for artificial agents to learn to behave with more human-like efficiency is taking working memory's role in learning seriously. This review highlights the risks of neglecting the interplay between different processes when studying human behavior (in particular when considering individual differences). We emphasize the importance of investigating these dynamics to build a comprehensive understanding of human cognition.
Paul among the Fluent in Corinth
Authors: Last Richard
Published: December 2021

This article foregrounds the importance of Paul’s letters for studying the experiences and perceptions of persons who stutter in antiquity. It analyzes Paul’s speech alongside the biographies of two other historical figures from antiquity who suffered from speech dysfluency: the great Athenian orator, Demosthenes, and the emperor Claudius. Accounts of Demosthenes’, Claudius’, and Paul’s speech inconsistencies, silences, incomprehensible utterances, oratory weaknesses—and their critics’ accusations that they suffered from madness—are interpreted in light of research on adults who stutter in the contemporary context, as well as studies on listener experiences and stereotypes. In introducing Paul into the study of ancient dysfluency, the article revisits Paul’s conflict with rival teachers in Corinth as it is in responding to these critics’ accusations that Paul is most revealing of his own dysfluency.
The Meaning of a Matthean Redaction
Authors: Blackburn Barry L.
Published: December 2021

In Matt 26:64 the evangelist redacts Mark 14:62 by adding the phrase ἀπ’ ἄρτι prior to Mark’s ὄψεσθε τὸν υἱὸν τοῦ ἀνθρώπου ἐξ δεξιῶν καθήµενον τῆς δυνάµεως καὶ ἐρχόµενον µετὰ τῶν νεφελῶν τoῦ οὐρανοῦ. The present study attempts to demonstrate (1) that this addition does not negate a reference to the parousia, as argued, inter alios, by John P. Meier and R.T. France, and (2) that ἀπ’ ἄρτι in Matt 26:64 functions to draw a sharp contrast between the humiliation of Jesus’ passion and his glorious parousia, which would happen in the near future.
South Sudan
Authors: Jok Jok Madut
Published: December 2021

When South Sudan gained independence in 2011, the whole world rejoiced. The country marked 10 years of independence on July 9, 2021, but on that occasion, as was the case for the previous decade, its people had very little to celebrate. The country had been gripped by both state violence and deadly ethnic feuds. The intense rifts in ethnic relations emanating from this cycle have become a major risk factor for mass atrocities. This paper aims to chronicle the atrocity crimes that have happened in South Sudan in the past 12 years, what drives them, and how they can be mitigated or stopped. It will also suggest what the international community can do to assist the South Sudanese to find justice, accountability for atrocity crimes and above all, how to reduce or end violence. The paper is based on a review of reports by human rights agencies, the United Nations agencies operating in South Sudan, independent researchers, academics and think tanks. It is also based on the author’s first-hand knowledge of the context and on numerous interviews with South Sudanese. The goal, however, is not to ask: what lessons have been learned from the ongoing efforts in the country?
An Insider’s Response to Racism: Abe Fortas and the Japanese Question during the Asia-Pacific War, 1941–1945
Authors: Lee Seok-Won
Published: December 2021

Abe Fortas (1910–1982) has been best known for service during his legal career as an Associate Justice on the Supreme Court of the United States for four years from 1965 to 1969. His supporters have characterized his life as a lawyer who supported and defended the American Civil Rights Movement during the tumultuous periods of the 1950s and 1960s in the United States. However, observers of his career have paid little attention to the fact that Fortas was one of the few American bureaucrats who took the stand in defense of those of Japanese ancestry in the official hearings in the 1980sinvestigating the internment of Japanese Americans during World War ii. Fortas, as undersecretary in the Department of the Interior from 1942 to 1946, had a close relationship to key U.S. policies dealing with people of Japanese ancestry during the Asia-Pacific War, including the establishment of martial law in Hawai‘i and the ending of the Japanese internment. Fortas’s responses to and critiques of U.S. policy regarding the Japanese American question reveal the intertwined dynamics of how white racism developed and challenges against it at the governmental level.
Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma
Authors: Bröske Ann-Marie E. , Korfi Koorosh , Belousov Anton , Wilson Sabine , Ooi Chia-Huey , Bolen Christopher R. , Canamero Marta , Alcaide Enrique Gomez , James Ian , Piccione Emily C. , Carlile David J. , Dimier Natalie , Umaña Pablo , Bacac Marina , Weisser Martin , Dickinson Michael
Published: December 2021

Glofitamab, a novel CD20xCD3, T-cell–engaging bispecific antibody, exhibited single-agent activity in Study NP30179, a first-in-human, phase 1 trial in relapsed/refractory B-cell non-Hodgkin lymphoma. Preclinical studies showed that glofitamab leads to T-cell activation, proliferation, and tumor cell killing upon binding to CD20 on malignant cells. Here, we provide evidence of glofitamab’s clinical activity, including pharmacodynamic profile, mode of action, and factors associated with clinical response, by evaluating biomarkers in patient samples from the dose-escalation part of this trial. Patients enrolled in Study NP30179 received single-dose obinutuzumab pretreatment (1000 mg) 7 days before IV glofitamab (5 µg-25 mg). Glofitamab treatment lasted ≤12 cycles once every 2 or 3 weeks. Blood samples were collected at predefined time points per the clinical protocol; T-cell populations were evaluated centrally by flow cytometry, and cytokine profiles were analyzed. Immunohistochemical and genomic biomarker analyses were performed on tumor biopsy samples. Pharmacodynamic modulation was observed with glofitamab treatment, including dose-dependent induction of cytokines, and T-cell margination, proliferation, and activation in peripheral blood. Gene expression analysis of pretreatment tumor biopsy samples indicated that tumor cell intrinsic factors such as TP53 signaling are associated with resistance to glofitamab, but they may also be interlinked with a diminished effector T-cell profile in resistant tumors and thus represent a poor prognostic factor per se. This integrative biomarker data analysis provides clinical evidence regarding glofitamab’s mode of action, supports optimal biological dose selection, and will further guide clinical development. This trial was registered at www.clinicaltrials.gov as #NCT03075696.
ERS/ATS technical standard on interpretive strategies for routine lung function tests
Authors: Stanojevic Sanja , Kaminsky David A. , Miller Martin R. , Thompson Bruce , Aliverti Andrea , Barjaktarevic Igor , Cooper Brendan G. , Culver Bruce , Derom Eric , Hall Graham L. , Hallstrand Teal S. , Leuppi Joerg D. , MacIntyre Neil , McCormack Meredith , Rosenfeld Margaret , Swenson Erik R.
Published: December 2021

Background

Appropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiological determinants of test results into functional classifications and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society (ATS) and European Respiratory Society (ERS) jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standards for PFT interpretation.

Methods

This technical standards document was developed by an international joint Task Force, appointed by the ERS/ATS with multidisciplinary expertise in conducting and interpreting PFTs and developing international standards. A comprehensive literature review was conducted and published evidence was reviewed.

Results

Recommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments.

Conclusions

Interpretation of PFTs must be complemented with clinical expertise and consideration of the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements.
Fine particulate matter components and interstitial lung disease in rheumatoid arthritis
Authors: Zhao Naizhuo , Al-Aly Ziyad , Zheng Boyang , van Donkelaar Aaron , Martin Randall V. , Pineau Christian A. , Bernatsky Sasha
Published: December 2021

Background

Exposure to ambient fine particulate matter with an aerodynamic diameter <2.5 μg·m−3(PM2.5) is a risk factor for pulmonary and systemic autoimmune diseases; however, evidence on which PM2.5chemical components are more harmful is still scant. Our goal is to investigate potential associations between major PM2.5components and interstitial lung disease (ILD) onset in rheumatoid arthritis (RA).

Methods

New-onset RA subjects identified from a US healthcare insurance database (MarketScan) were followed for new onset of RA-associated ILD (RA-ILD) from 2011 to 2018. Annual concentrations of ambient PM2.5chemical components (i.e.sulfate, nitrate, ammonium, organic matter, black carbon, mineral dust and sea salt) were estimated by combining satellite retrievals with chemical transport modelling and refined by geographically weighted regression. Exposures from 2006 up to 1 year before ILD onset or end of study were assigned to subjects based on their core-based statistical area or metropolitan division codes. A novel time-to-event quantile-based g (generalised)-computation approach was used to estimate potential associations between RA-ILD onset and the exposure mixture of all seven PM2.5chemical components adjusting for age, sex and prior chronic obstructive pulmonary disease (as a proxy for smoking).

Results

We followed 280 516 new-onset RA patients and detected 2194 RA-ILD cases across 1 394 385 person-years. The adjusted hazard ratio for RA-ILD onset was 1.54 (95% CI 1.47–1.63) per every decile increase in all seven exposures. Ammonium, mineral dust and black carbon contributed more to ILD risk than the other PM2.5components.

Conclusion

Exposure to components of PM2.5, particularly ammonium, increases ILD risk in RA.
Predicting in-hospital death in pneumonic COPD exacerbationviaBAP-65, CURB-65 and machine learning
Authors: Shiroshita Akihiro , Kimura Yuya , Shiba Hiroshi , Shirakawa Chigusa , Sato Kenya , Matsushita Shinya , Tomii Keisuke , Kataoka Yuki
Published: December 2021

Introduction

There is no established clinical prediction model for in-hospital death among patients with pneumonic COPD exacerbation. We aimed to externally validate BAP-65 and CURB-65 and to develop a new model based on the eXtreme Gradient Boosting (XGBoost) algorithm.

Methods

This multicentre cohort study included patients aged ≥40 years with pneumonic COPD exacerbation. The input data were age, sex, activities of daily living, mental status, systolic and diastolic blood pressure, respiratory rate, heart rate, peripheral blood eosinophil count and blood urea nitrogen. The primary outcome was in-hospital death. BAP-65 and CURB-65 underwent external validation using the area under the receiver operating characteristic curve (AUROC) in the whole dataset. We used XGBoost to develop a new prediction model. We compared the AUROCs of XGBoost with that of BAP-65 and CURB-65 in the test dataset using bootstrap sampling.

Results

We included 1190 patients with pneumonic COPD exacerbation. The in-hospital mortality was 7% (88 out of 1190). In the external validation of BAP-65 and CURB-65, the AUROCs (95% confidence interval) of BAP-65 and CURB-65 were 0.69 (0.66–0.72) and 0.69 (0.66–0.72), respectively. XGBoost showed an AUROC of 0.71 (0.62–0.81) in the test dataset. There was no significant difference in the AUROCs of XGBoostversusBAP-65 (absolute difference 0.054; 95% CI −0.057–0.16) orversusCURB-65 (absolute difference 0.0021; 95% CI −0.091–0.088).

Conclusion

BAP-65, CURB-65 and XGBoost showed low predictive performance for in-hospital death in pneumonic COPD exacerbation. Further large-scale studies including more variables are warranted.
Sarcopenia, systemic immune-inflammation index and all-cause mortality in middle-aged and older people with COPD and asthma: a population-based study
Authors: Benz Elizabeth , Wijnant Sara R.A. , Trajanoska Katerina , Arinze Johnmary T. , de Roos Emmely W. , de Ridder Maria , Williams Ross , van Rooij Frank , Verhamme Katia M.C. , Ikram M. Arfan , Stricker Bruno H. , Rivadeneira Fernando , Lahousse Lies , Brusselle Guy G.
Published: December 2021

Background

Increasing evidence suggests that sarcopenia and a higher systemic immune-inflammation index (SII) are linked with morbidity in patients with COPD. However, whether these two conditions contribute to all-cause mortality in middle-aged and older patients with COPD or asthma is unclear. Therefore, we investigated the association between sarcopenia, SII, COPD or asthma and all-cause mortality in a large-scale population-based setting.

Methods

Between 2009 and 2014, 4482 participants (aged >55 years; 57.3% female) from the population-based Rotterdam Study were included. COPD and asthma patients were diagnosed clinically and based on spirometry. Six study groups were defined according to the presence or absence of COPD or asthma and sarcopenia. Cox regression models were used to assess all-cause mortality in the study groups, adjusted for sex, age, body mass index, SII, smoking, oral corticosteroid use and comorbidities. In addition, all participants were categorised into sex-specific quartiles of SII, and mortality in these groups was compared.

Results

Over a median follow-up of 6.1 years (interquartile range 5.0–7.2 years), 466 (10.4%) persons died. Independent of the presence of sarcopenia, participants with COPD had a higher risk of all-cause mortality (hazard ratio (HR) 2.13, 95% CI 1.46–3.12 and HR 1.70, 95% CI 1.32–2.18 for those with and without sarcopenia, respectively). Compared to lower SII levels, higher SII levels increased mortality risk even in people without sarcopenia, COPD or asthma.

Conclusion

Middle-aged and older people with COPD, higher SII levels or sarcopenia had an independently increased mortality risk. Our study suggests prognostic usefulness of routinely evaluating sarcopenia and SII in older people with COPD or asthma.
Delayed-onset post-operative keratitis and endophthalmitis caused by Exophiala oligosperma
Authors: van der Merwe Laurie W. , da Costa Dawood , Reddy Kessendri , Meyer David
Published: December 2021

A case of delayed-onset post-cataract-surgery keratitis and endophthalmitis, caused by the melanin-producing fungus Exophiala oligosperma, is presented. The patient presented with an infection at the corneal side-port wound 5 months after an uneventful phacoemulsification surgery. Despite pars plana vitrectomy and combination antifungal treatment, the patient required an evisceration of the globe. Limited clinical information is available about the treatment of eye infections caused by this organism.
GeneTonic: an R/Bioconductor package for streamlining the interpretation of RNA-seq data
Authors: Marini Federico , Ludt Annekathrin , Linke Jan , Strauch Konstantin
Published: December 2021

Background

The interpretation of results from transcriptome profiling experiments via RNA sequencing (RNA-seq) can be a complex task, where the essential information is distributed among different tabular and list formats—normalized expression values, results from differential expression analysis, and results from functional enrichment analyses. A number of tools and databases are widely used for the purpose of identification of relevant functional patterns, yet often their contextualization within the data and results at hand is not straightforward, especially if these analytic components are not combined together efficiently.

Results

We developed the software package, which serves as a comprehensive toolkit for streamlining the interpretation of functional enrichment analyses, by fully leveraging the information of expression values in a differential expression context. is implemented in R and Shiny, leveraging packages that enable HTML-based interactive visualizations for executing drilldown tasks seamlessly, viewing the data at a level of increased detail. is integrated with the core classes of existing Bioconductor workflows, and can accept the output of many widely used tools for pathway analysis, making this approach applicable to a wide range of use cases. Users can effectively navigate interlinked components (otherwise available as flat text or spreadsheet tables), bookmark features of interest during the exploration sessions, and obtain at the end a tailored HTML report, thus combining the benefits of both interactivity and reproducibility.

Conclusion

is distributed as an R package in the Bioconductor project (https://bioconductor.org/packages/GeneTonic/) under the MIT license. Offering both bird’s-eye views of the components of transcriptome data analysis and the detailed inspection of single genes, individual signatures, and their relationships, aims at simplifying the process of interpretation of complex and compelling RNA-seq datasets for many researchers with different expertise profiles.
Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus
Authors: Shimizu Hiromichi , Fujii Toshimitsu , Kinoshita Kenji , Kawamoto Ami , Hibiya Shuji , Takenaka Kento , Saito Eiko , Nagahori Masakazu , Ohtsuka Kazuo , Watanabe Mamoru , Okamoto Ryuichi
Published: December 2021

Background

Intravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied.

Aim

To determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis.

Methods

Eighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks.

Results

Response rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus.

Conclusions

Patients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments.
Understanding the determinants of postnatal care uptake for babies: A mixed effects multilevel modelling of 2016–18 Papua New Guinea Demographic and Health Survey
Authors: Appiah Francis , Fenteng Justice Ofosu Darko , Dare Felix , Salihu Tarif , Darteh Andrews Ohene , Takyi Matthew , Ayerakwah Patience Ansomah , Ameyaw Edward Kwabena
Published: December 2021

Background

Papua New Guinea (PNG) recorded 22 neonatal deaths out of every 1,000 livebirths in 2019. Some of these deaths are related to complications that arise shortly after childbirth; hence, postnatal care (PNC) utilisation could serve as a surviving strategy for neonates as recommended by the World Health Organisation. National level study on determinants of PNC uptake in PNG is limited. Utilising the Bronfenbrenner’s Ecological Model of Human Development, the study aimed at assessing determinants of PNC utilisation for babies by their mothers aged 15–49 in PNG.

Methods

The study used data from the women’s file of the 2016–18 PNG Demographic and Health Survey (2016–18 PNGDHS) and a sample of 4,908 women aged 15–49 who had complete information on the variables of interest to the study. Nineteen (19) explanatory variables were selected for the study whereas PNC for babies within first two months after being discharged after birth was the main outcome variable. At 95% confidence interval (95% CI), six multilevel logistic models were built. The Akaike Information Criterion (AIC) was used to assess models’ fit. All analyses were carried out using STATA version 14.0.

Results

Generally, 31% of the women utilised PNC for their babies. Women with primary education [aOR = 1.42, CI = 1.13–1.78], those belonging to the middle wealth quintile [aOR = 1.42, CI = 1.08–1.87], working class [aOR = 1.28, CI = 1.10–1.49], women who had the four or more ANC visits [aOR = 1.23, CI = 1.05–1.43], those with twins [aOR = 1.83, CI = 1.01–3.29], women who belonged to community of medium literate class [aOR = 1.75, CI = 1.34–2.27] and those of moderate socioeconomic status [aOR = 1.60, CI = 1.16–2.21] had higher odds of seeking PNC for their babies. The odds to seek PNC services for babies reduced among the cohabiting women [aOR = 0.79, CI = 0.64–0.96], those at parity four or more [aOR = 0.77, CI = 0.63–0.93], women who gave birth to small babies [aOR = 0.80, CI = 0.67–0.98] and residents in the Highlands region [aOR = 0.47, CI = 0.36–0.62].

Conclusions

Maternal education, wealth quintile, occupation, partner’s education, ANC visits, marital status, parity, child size at birth, twin status, community literacy and socioeconomic status as well as region of residence were associated with PNC uptake for babies in PNG. Variation in PNC uptake for babies existed from one community/cluster to the other. There is the need to strengthen public health education to increase awareness about the benefits of seeking PNC services for babies among women in PNG. Such programs should consider maternal and community/cluster characteristics in their design.
History of drinking problems diminishes the protective effects of within-guideline drinking on 18-year risk of dementia and CIND
Authors: Brennan Penny L. , Holahan Charles J. , Moos Rudolf H. , Schutte Kathleen K.
Published: December 2021

Objective

To examine the moderating effect of older adults’ history of drinking problems on the relationship between their baseline alcohol consumption and risk of dementia and cognitive impairment, no dementia (CIND) 18 years later.

Method

A longitudinal Health and Retirement Study cohort (n = 4421) was analyzed to demonstrate how older adults’ baseline membership in one of six drinking categories (non-drinker, within-guideline drinker, and outside-guideline drinker groups, divided to reflect absence or presence of a history of drinking problems) predicts dementia and CIND 18 years later.

Results

Among participants with no history of drinking problems, 13% of non-drinkers, 5% of within-guideline drinkers, and 9% of outside-guideline drinkers were classified as having dementia 18-years later. Among those with a history of drinking problems, 14% of non-drinkers, 9% of within-guideline drinkers, and 7% of outside-guideline drinkers were classified with dementia. With Non-Drinker, No HDP as reference category, being a baseline within-guideline drinker with no history of drinking problems reduced the likelihood of dementia 18 years later by 45%, independent of baseline demographic and health characteristics; being a baseline within-guideline drinker with a history of drinking problems reduced the likelihood by only 13% (n.s.). Similar patterns obtained for the prediction of CIND.

Conclusions

For older adults, consuming alcohol at levels within validated guidelines for low-risk drinking may offer moderate long-term protection from dementia and CIND, but this effect is diminished by having a history of drinking problems. Efforts to predict and prevent dementia and CIND should focus on older adults’ history of drinking problems in addition to how much alcohol they consume.
Factors associated with antihypertensive medication use and blood pressure control in a rural area in Bangladesh: baseline data from a cluster randomised control trial
Authors: Amirul Islam Fakir M. , Lambert Elisabeth A. , Islam Sheikh Mohammed Shariful , Islam M. Ariful , Maddison Ralph , Thompson Bruce , Lambert Gavin W.
Published: December 2021

Background

The use of antihypertensive medications is critical for controlling high blood pressure. We aimed to investigate associations between socio-demographic factors and antihypertensive medications use, and antihypertensive medications use with different types of drugs use with levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP).

Methods

For the present report we derived data from the baseline measurements of a cluster randomised control trial on 307 participants with previously diagnosed hypertension from the rural district of Narial in Bangladesh. We measured the participant’s current blood pressure levels and recorded antihypertensive medications uses. Associated factors included socio-economic status, diabetes, antihypertensive medications use, and types of drugs and doses used for controlling blood pressure. We applied analysis of variance and logistic regression techniques to identify factors associated with blood pressure.

Results

Of the total participants, 144 (46.9%) were on antihypertensive medications. After multivariate adjustment, binary logistic regression revealed that employees (odds ratio, (95% confidence interval (CI)) (OR 3.58, 95%CI 1.38-9.28) compared to farmers, and people with diabetes (OR 2.43, 95%CI 1.13-5.26) compared to people without diabetes were associated with a higher proportion of antihypertensive medications use. Of 144 participants on antihypertensive medications, 7 (5%) had taken two doses, 114 (79%) had taken one dose per day and the rest were irregular in medication use. The mean (standard deviation) [min, max] SBP and DBP were 149 (19) mmHg [114, 217] and 90 (10) mmHg [75, 126], respectively. Overall, there was no significant difference in SBP (p = 0.10) or DBP (p = 0.67) between participants with or without antihypertensive medications or using any type of medications (p = 0.54 for SBP and 0.76 for DBP). There was no significant association between antihypertensive medications use and elevated BP levels SBP/DBP≥140/90 mmHg (p = 0.42)

Conclusion

Less than half of the people with hypertension were on medication. Irrespective of the antihypertensive medications use, most of the participant’s blood pressure was high. Further study is needed with a large sample to understand the factors and aetiology of unmanaged hypertension in rural areas of Bangladesh where the prevalence of hypertension is very high.