bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of DNA Double-Strand Break Formation by DNA Polymerase β in Active DNA Demethylation Is Required for Development of Hippocampal Pyramidal Neurons
Authors: Uyeda Akiko , Onishi Kohei , Hirayama Teruyoshi , Hattori Satoko , Miyakawa Tsuyoshi , Yagi Takeshi , Yamamoto Nobuhiko , Sugo Noriyuki 
Published: October 2020

Genome stability is essential for brain development and function, asde novomutations during neuronal development cause psychiatric disorders. However, the contribution of DNA repair to genome stability in neurons remains elusive. Here, we demonstrate that the base excision repair protein DNA polymerase β (Polβ) is involved in hippocampal pyramidal neuron differentiation via a TET-mediated active DNA demethylation during early postnatal stages usingNex-Cre/Polβfl/flmice of either sex, in which forebrain postmitotic excitatory neurons lack Polβ expression. Polβ deficiency induced extensive DNA double-strand breaks (DSBs) in hippocampal pyramidal neurons, but not dentate gyrus granule cells, and to a lesser extent in neocortical neurons, during a period in which decreased levels of 5-methylcytosine and 5-hydroxymethylcytosine were observed in genomic DNA. Inhibition of the hydroxylation of 5-methylcytosine by expression of microRNAs miR-29a/b-1 diminished DSB formation. Conversely, its induction by TET1 catalytic domain overexpression increased DSBs in neocortical neurons. Furthermore, the damaged hippocampal neurons exhibited aberrant neuronal gene expression profiles and dendrite formation, but not apoptosis. Comprehensive behavioral analyses revealed impaired spatial reference memory and contextual fear memory in adulthood. Thus, Polβ maintains genome stability in the active DNA demethylation that occurs during early postnatal neuronal development, thereby contributing to differentiation and subsequent learning and memory.SIGNIFICANCE STATEMENTIncreasing evidence suggests thatde novomutations during neuronal development cause psychiatric disorders. However, strikingly little is known about how DNA repair is involved in neuronal differentiation. We found that Polβ, a component of base excision repair, is required for differentiation of hippocampal pyramidal neurons in mice. Polβ deficiency transiently led to increased DNA double-strand breaks, but not apoptosis, in early postnatal hippocampal pyramidal neurons. This aberrant double-strand break formation was attributed to active DNA demethylation as an epigenetic regulation. Furthermore, the damaged neurons exhibited aberrant gene expression profiles and dendrite formation, resulting in impaired learning and memory in adulthood. Thus, these findings provide new insight into the contribution of DNA repair to the neuronal genome in early brain development.
Structure of Population Activity in Primary Motor Cortex for Single Finger Flexion and Extension
Authors: Arbuckle Spencer A. , Weiler Jeff , Kirk Eric A. , Rice Charles L. , Schieber Marc , Pruszynski J. Andrew , Ejaz Naveed , Diedrichsen Jörn 
Published: October 2020

How is the primary motor cortex (M1) organized to control fine finger movements? We investigated the population activity in M1 for single finger flexion and extension, using 7T functional magnetic resonance imaging (fMRI) in female and male human participants and compared these results to the neural spiking patterns recorded in two male monkeys performing the identical task. fMRI activity patterns were distinct for movements of different fingers, but were quite similar for flexion and extension of the same finger. In contrast, spiking patterns in monkeys were quite distinct for both fingers and directions, which is similar to what was found for muscular activity patterns. The discrepancy between fMRI and electrophysiological measurements can be explained by two (non-mutually exclusive) characteristics of the organization of finger flexion and extension movements. Given that fMRI reflects predominantly input and recurrent activity, the results can be explained by an architecture in which neural populations that control flexion or extension of the same finger produce distinct outputs, but interact tightly with each other and receive similar inputs. Additionally, neurons tuned to different movement directions for the same finger (or combination of fingers) may cluster closely together, while neurons that control different finger combinations may be more spatially separated. When measuring this organization with fMRI at a coarse spatial scale, the activity patterns for flexion and extension of the same finger would appear very similar. Overall, we suggest that the discrepancy between fMRI and electrophysiological measurements provides new insights into the general organization of fine finger movements in M1.SIGNIFICANCE STATEMENTThe primary motor cortex (M1) is important for producing individuated finger movements. Recent evidence shows that movements that commonly co-occur are associated with more similar activity patterns in M1. Flexion and extension of the same finger, which never co-occur, should therefore be associated with distinct representations. However, using carefully controlled experiments and multivariate analyses, we demonstrate that human fMRI activity patterns for flexion or extension of the same finger are highly similar. In contrast, spiking patterns measured in monkey M1 are clearly distinct. This suggests that populations controlling opposite movements of the same finger, while producing distinct outputs, may cluster together and share inputs and local processing. These results provide testable hypotheses about the organization of hand control in M1.
Entraining Stepping Movements of Parkinson's Patients to Alternating Subthalamic Nucleus Deep Brain Stimulation
Authors: Fischer Petra , He Shenghong , de Roquemaurel Alexis , Akram Harith , Foltynie Thomas , Limousin Patricia , Zrinzo Ludvic , Hyam Jonathan , Cagnan Hayriye , Brown Peter , Tan Huiling 
Published: October 2020

Patients with advanced Parkinson's can be treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). This affords a unique opportunity to record from this nucleus and stimulate it in a controlled manner. Previous work has shown that activity in the STN is modulated in a rhythmic pattern when Parkinson's patients perform stepping movements, raising the question whether the STN is involved in the dynamic control of stepping. To answer this question, we tested whether an alternating stimulation pattern resembling the stepping-related modulation of activity in the STN could entrain patients' stepping movements as evidence of the STN's involvement in stepping control. Group analyses of 10 Parkinson's patients (one female) showed that alternating stimulation significantly entrained stepping rhythms. We found a remarkably consistent alignment between the stepping and stimulation cycle when the stimulation speed was close to the stepping speed in the five patients that demonstrated significant individual entrainment to the stimulation cycle. Our study suggests that the STN is causally involved in dynamic control of step timing and motivates further exploration of this biomimetic stimulation pattern as a potential basis for the development of DBS strategies to ameliorate gait impairments.SIGNIFICANCE STATEMENTWe tested whether the subthalamic nucleus (STN) in humans is causally involved in controlling stepping movements. To this end, we studied patients with Parkinson's disease who have undergone therapeutic deep brain stimulation (DBS), as in these individuals we can stimulate the STNs in a controlled manner. We developed an alternating pattern of stimulation that mimics the pattern of activity modulation recorded in this nucleus during stepping. The alternating DBS (altDBS) could entrain patients' stepping rhythm, suggesting a causal role of the STN in dynamic gait control. This type of stimulation may potentially form the basis for improved DBS strategies for gait.
Preoperative Blood Transfusions and Morbidity in Neonates Undergoing Surgery
Authors: Dukleska Katerina , Vinocur Charles D. , Brenn B. Randall , Lim Doyle J. , Keith Scott W. , Dirnberger Daniel R. , Berman Loren 
Published: October 2020

BACKGROUND:
Blood transfusions in the neonatal patient population are common, but there are no established guidelines regarding transfusion thresholds. Little is known about postoperative outcomes in neonates who receive preoperative blood transfusions (PBTs).

METHODS:
Using the American College of Surgeons National Surgical Quality Improvement Program–Pediatric Participant Use Data Files from 2012 to 2015, we identified all neonates who underwent surgery. Mortality and composite morbidity (defined as any postoperative complication) in neonates who received a PBT within 48 hours of surgery were compared with that in neonates who did not receive a transfusion.

RESULTS:
A total of 12 184 neonates were identified, of whom 1209 (9.9%) received a PBT. Neonates who received a PBT had higher rates of preoperative comorbidities and worse postoperative outcomes when compared with those who did not receive a transfusion (composite morbidity: 46.2% vs 16.2%; P &lt; .01). On multivariable regression analysis, PBTs were independently associated with increased 30-day morbidity (odds ratio [OR] = 1.90; 95% confidence interval [CI]: 1.63–2.22; P &lt; .01) and mortality (OR = 1.98; 95% CI: 1.55–2.55; P &lt; .01). In a propensity score–matched analysis, PBTs continued to be associated with increased 30-day morbidity (OR = 1.53; 95% CI: 1.29–1.81; P &lt; .01) and mortality (OR = 1.58; 95% CI: 1.24–2.01; P = .01).

CONCLUSIONS:
In a propensity score–matched model, PBTs are independently associated with increased morbidity and mortality in neonates who undergo surgery. Prospective data are needed to better understand the potential effects of a red blood cell transfusion in this patient population.
Guidelines on Deferred Cord Clamping and Cord Milking: A Systematic Review
Authors: Liyanage Sugee Korale , Ninan Kiran , McDonald Sarah D. 
Published: October 2020

CONTEXT:
Deferred cord clamping (DCC) saves lives. It reduces extremely preterm infants’ mortality by 30%, yet a minority of eligible infants receive it. This may in part be due to lack of awareness or confidence in evidence, or conflicting or vague guidelines.

OBJECTIVE:
To systematically review clinical practice guidelines and other statements on DCC and cord milking.

DATA SOURCES:
Ten academic and guideline databases were searched.

STUDY SELECTION:
Clinical practice guidelines and other statements (position statements and consensus statements) providing at least 1 recommendation on DCC or umbilical cord milking among preterm or term infants were included.

DATA EXTRACTION:
Data from included statements were extracted by 2 independent reviewers, and discrepancies were resolved through consensus. Guideline quality was appraised with modified Appraisal of Guidelines for Research and Evaluation II and Appraisal of Guidelines for Research and Evaluation Recommendation Excellence tools.

RESULTS:
Forty-four statements from 35 organizations were included. All endorsed DCC for uncompromised preterm infants, and 11 cautiously stated that cord milking may be considered when DCC is infeasible. Only half (49%) of the recommendations on the optimal duration of DCC were supported by high-quality evidence. Only 8% of statements cited a mortality benefit of DCC for preterm infants.

LIMITATIONS:
Because systematic reviews of guidelines are relatively novel, there are few tools to inform study execution; however, we used the Appraisal of Guidelines for Research and Evaluation II and the Appraisal of Guidelines for Research and Evaluation Recommendation Excellence to assess quality and were methodologically informed by previous systematic reviews of guidelines.

CONCLUSIONS:
Statements worldwide clearly encouraged DCC. Their implementability would benefit from noting the preterm mortality benefit of DCC and more granularity.
Gaitada Gizli Kan Pozitifliği Nedeniyle Kolonoskopi Yapılanlarda Kolorektal Malignite Sıklığı
Authors: AKKUZU Mustafa Zanyar , SEZGİN Orhan , ÜÇBİLEK Enver , ÖZDOĞAN Osman , AYDIN Ferzan , RIZAOĞLU BALCI Hatice , YARAŞ Serkan , ATES Fehmi , ALTİNTAS Engin 
Published: October 2020

Giriş ve Amaç: Kolorektal kanserlerin erken evrede belirlenmesi, prognozun iyileştirilmesindeki en önemli kısımdır. Bunun yolu etkili tarama programlarından geçmektedir. Gaitada gizli kan (GGK) testi tarama yöntemlerinin başında gelmektedir. Bu çalışmada endoskopi ünitemizde GGK testi pozitifliği nedeniyle kolonoskopi yapılan hastalarda kolonoskopik bulguları değerlendirmeyi, polip sıklığını, histopatolojik tiplerini ve kolorektal malignite sıklığını saptamayı amaçladık.
Materyal ve Metod: 2018 Aralık ve 2019 Temmuz ayları arasında GGK pozitif olup etyoloji araştırılması nedeniyle kolonoskopi yapılan hastalar çalışmaya alındı. Kolonoskopi uygun hazırlık sonrası terminal ileum da değerlendirilecek şekilde uygulanmıştı. Hastaların yaş, cinsiyet, anamnez bilgileri, kolonoskopi ve patoloji sonuçlarına dosya bilgileri araştırılarak geriye dönük olarak ulaşıldı.
Bulgular: Bu sürede GGK pozitifliği nedeniyle 70 hastaya kolonoskopi yapılmıştı. Hastaların 36 (%51)’sı erkek, 34 (% 49)’ü kadındı. Erkeklerin yaş ortalaması 50,1±14,8, kadınların yaş ortalaması 54,6 ± 13,9 idi. Olguların 13 (%19)’ünde adenomatöz polip, 4 (%5,7)’ünde adenokarsinom ve birinde (%1,4) malign melanom tespit edildi. Polip tespit edilen 7 erkek ve 6 kadın hastanın yaş ortalamaları 61,5±9 idi. Poliplerin %76’sı sol kolonda, malignitelerin %80’i rektosigmoid kolonda idi. Olguların %74’ünde GGK pozitifliğini açıklayacak bir patoloji saptanmamıştı. Poliplerin tamamı kolonoskopik yöntemlerle başarıyla çıkarılmıştı.
Tartışma ve Sonuç: GGK pozitifliği nedeniyle kolonoskopi yapılan olguların %7’sinde kolorektal malignite ve %19’unda adenomatöz polip saptanması GGK testi pozitifliğinin önemini göstermektedir. Tarama programları sayesinde kolorektal kanserler ve prekanseröz lezyonların erken teşhis edilip, sağ kalım oranlarının artabileceği görülmektedir.
Wpływ niezrównoważonego przyrostu naturalnego w południowym sąsiedztwie Europy na występowanie konfliktów wewnętrznych i regionalnych
Authors: Repetowicz Witold 
Published: October 2020

Przyrost ludności na Bliskim Wschodzie i w Afryce jest nie tylko większy niż w Europie, ale również niezrównoważony w wymiarze regionalnym. Oznacza to, że proporcje populacji w odniesieniu do poszczególnych państw, a także grup etnicznych, religijnych i plemiennych, podlegają procesowi poważnych zmian i ta tendencja będzie kontynuowana w najbliższych dekadach. Ponieważ populacja jest fundamentalnym elementem potęgi państw, będzie więc miała nie tylko konsekwencje wewnętrzne, ale też wpływ na układ geopolityczny. Gwałtowny przyrost ludności może z jednej strony osłabić i zdestabilizować niektóre państwa, jeśli ich rządy nie będą zdolne do odpowiedniego nim zarządzania, zwłaszcza w zakresie zatrudnienia. Populacja może być również wykorzystana do regionalnej rywalizacji, zagrożenia innych państw strumieniem migracyjnym, a także wyzwań o charakterze militarnym. Wpływ niezrównoważonego przyrostu ludności na Bliskim Wschodzie na regionalną stabilność nie napawa optymizmem. Najprawdopodobniej będzie on prowadził do nowej regionalnej rywalizacji według podziałów sektariańskich i etnicznych, a także geopolitycznej rywalizacji poszczególnych państw o potęgę. Przyrost ludności dwóch spośród trzech najludniejszych państw regionu, tj. Turcji i Iranu, szybko spada. Jest to ważne również dlatego, że te państwa pretendują do roli mocarstw regionalnych. Z drugiej strony największy przyrost ludności na Bliskim Wschodzie występuje w Iraku, który jest uważany za państwo słabe, o ile nie upadłe. Nierozwiązane problemy etniczne, w szczególności kwestia kurdyjska i palestyńska, dodatkowo przyczynią się do niepewności co do perspektywy stabilności i prawdopodobieństwa eskalacji starych konfliktów, zwłaszcza że przyrost ludności wśród tych grup jest wyższy niż w regionie. W Afryce niezrównoważony przyrost ludności może powodować konflikty plemienne. Bliskość Europy i wysokie prawdopodobieństwo migracji z obszarów objętych konfliktami powoduje, że niezrównoważony przyrost ludności i jego konsekwencje na Bliskim Wschodzie i w Afryce będą również wyzwaniem dla stabilności oraz bezpieczeństwa Europy.
Estudo sobre a utilização racional de medicamentos em idosos
Authors: Silva Rodrigo Rodrigues , Campos Marília Silveira de Almeida , Pereira Leonardo Régis Leira , Santos Álvaro Da Silva 
Published: October 2020

Este estudo teve como objetivo analisar as Interações Medicamentosas Potenciais e os Medicamentos Potencialmente Inapropriados para Idosos usuários das farmácias da atenção primária. Estudo descritivo com desenho transversal com amostra de 384 idosos/cuidadores, distribuídos entre todas as seis farmácias da cidade de Uberaba, MG no ano de 2015. Todas as prescrições apresentadas foram analisadas e os medicamentos classificados segundo a Anatomical Therapeutic Chemical Classification; e, na base de dados MICROMEDEX® e pelo Critério de Beers-Fick (2015). Foram analisadas 580 prescrições e verificadas 570 Interações, estando 47,4% dos participantes sujeitos a pelo menos uma interação; 54,7% utilizavam medicamentos inapropriados. Os medicamentos mais envolvidos nas interações foram: omeprazol (19,5%), AAS (14,2%) e losartana (13,2%). Verificou-se a necessidade de adoção de medidas gerenciais e educativas que visem mais segurança e eficácia terapêutica para os idosos.
Multifunctional Foaming Agents for Production Enhancement in Oil Wells: Field Test Results
Authors: Parra José Ernesto , Rosales Arias Fermín , Soto-Castruita Enrique , Jiménez de la Cruz Guillermo , Ramírez-Pérez Jorge Francisco , Cerón-Camacho Ricardo , Cisneros-Dévora Rodolfo , Servín-Nájera Ana Graciela , Zamudio-Rivera Luis Silvestre 
Published: October 2020

Abstract
We describe the first field applications of a new multifunctional foaming agent (MFA) for production enhancement in oil wells with gas lift. The tests were conducted in three wells with water cuts from 40 to 90%, depth (&gt;5000 m), bottomhole temperature (150°C), and brine hardness and salinity up to 180,000 ppm and 310,000 ppm TDS, respectively. The MFA was coinjected with lift gas via the annulus and generated foam downhole as it mixed with reservoir fluids in the tubing. Tested MFA concentrations ranged from 160 to 750 ppm. The field tests demonstrated that the MFA was able to increase the oil production for a fixed gas lift injection volume. The MFA also enabled to reduce lift gas consumption, while maintaining or even increasing the original oil production.
Performance of Mattis dementia rating scale-Chinese Version in patients with mild cognitive impairment and Alzheimer's disease
Authors: Qian Shuxia , Chen Keliang , Guan Qiaobing , Guo Qihao 
Published: October 2020

Abstract
Background: To identify the applicability of the Chinese Version of Mattis Dementia Rating Scale (DRS-CV).Methods: The DRS-CV was administered to 483 participants, including 136 normal controls, 167 patients with mild cognition impairment (MCI), and 180 patients with Alzheimer’s disease (AD). Receiver Operating Characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the scale.Results: The scores of DRS-CV were ranked in the order of NC >MCI > mild AD > moderate AD group. Memory was the sensitive function affected at a relatively earlier stage of AD. ROC curve analysis indicated the DRS-CV total score and memory subscale showed excellent sensitivity and specificity in the discrimination between MCI from mild AD and mild AD from moderate AD, but poor sensitivity and specificity in the discrimination between MCI and NC.Conclusion: The DRS-CV is useful to the early diagnosis and severity of AD, not to the early identification of MCI.
KPNA2 expression is a potential marker for differential diagnosis between osteosarcomas and other malignant bone tumor mimics
Authors: Jiang Lucen , Liu Jianghuan , Wei Qingzhu , Wang Yiyang 
Published: October 2020

Abstract
Background: Karyopherin α2 (KPNA2), a member of the karyopherin α family, has been studied in several cancers but has not yet been substantially investigated in malignant bone tumors. The purpose of the current study was to evaluate the KPNA2 expression level and its utility as a novel diagnostic biomarker in osteosarcomas and malignant bone tumor mimics, such as chondrosarcomas and Ewing sarcomas (ESs).Method: We investigated the expression of KPNA2 protein by immunohistochemistry on paraffin-embedded surgical specimens from 223 patients with malignant and benign bone tumors, including 81 osteosarcomas, 42 chondrosarcomas, 15 ESs, 28 osteoid osteomas, 20 osteochondromas and 37 chondroblastomas. Immunoreactivity was scored semiquantitatively based on staining extent and intensity.Results: Sixty-seven of 81 (82.7%) osteosarcoma, zero of 42 (0%) chondrosarcoma and one of 15 (6.7%) ES samples showed immunoreactivity for KPNA2. Negative KPNA2 expression was observed in all benign bone tumors. The expression of KPNA2 in osteosarcoma samples was much higher than that in chondrosarcoma and ES samples (P<0.001). The sensitivity and specificity of KPNA2 immunoexpression for detecting osteosarcoma were 82.7% and 100%, respectively. Several subtypes of osteosarcoma were analyzed, and immunostaining of KPNA2 was frequent in osteoblastic samples (90.9%), with 39 samples (70.9%) showing strong-intensity staining. KPNA2 positivity was observed in ten of 13 (76.9%) chondroblastic, two of 6 (33.3%) fibroblastic, three of 4 (75%) telangiectatic and two of 3 (66.7%) giant cell-rich osteosarcoma samples. The strongest intensity staining was observed in osteoblastic osteosarcoma.Conclusion: KPNA2 is frequently expressed in osteosarcomas, particularly in osteoblastic and chondroblastic tumors, but is rarely positive in chondrosarcomas and ESs. This feature may aid in distinguishing between osteosarcoma and other bone sarcoma mimics. This report supports KPNA2 as a novel marker for the diagnosis of osteosarcoma.