bluuebunny/crossref_metadata_2025 huggingface dataset:
A extensão universitária no Brasil e seus desafios durante a pandemia da COVID-19
Authors: Mélo Cláudia Batista , Farias Gabrieli Duarte , Nunes Vitória Régia Rolim , Andrade Tifany Shela Albuquerque Borba de , Piagge Carmem Silvia Laureano Dalle
Published: March 2021

O cenário atual, permeado por desafios devido à pandemia da COVID-19, fez com que as ações extensionistas promovidas por Instituições de Ensino Superior (IES) brasileiras tivessem que se readequar. O objetivo deste estudo é retratar os caminhos percorridos por tais instituições para adaptar ações já existentes e desenvolver novas que atendessem às necessidades encontradas. Esse trabalho caracteriza-se como pesquisa documental, descritiva, qualitativa e quantitativa sobre a extensão acadêmica durante a pandemia da COVID-19. Utilizou-se dados primários, em domínio público, como editais, regulamentos e notícias disponíveis nos websites das instituições, buscando-se responder variáveis pré-estabelecidas. A população (129) abarcou as IES federais e estaduais disponibilizadas no website do e-MEC, sendo a amostra 126. Como parte dos resultados encontrados, 87,5% das IES públicas optaram por continuar as ações de extensão durante 2020, com 87,9% sendo adaptadas e 71,8% com flexibilização das normas. As modalidades extensionistas, tais como projetos (90,3%), programas (75%), cursos (78,2%) e eventos (75%), foram expressivamente realizadas. Todavia, apenas 51% das IES apresentaram prestação de serviços. Ações destinadas ao enfrentamento da COVID-19 envolveram disponibilização de informações (34%), confecção/entrega de materiais destinados a prevenção (12%) e realização de atendimento aos casos (4%). 24% das instituições publicaram edital de extensão com vigência para 2021 com adequações à pandemia, enquanto 38% publicaram edital sem adequações. Conclui-se que a extensão foi adaptada às necessidades desencadeadas pela pandemia da COVID-19 e ações de enfrentamento foram desenvolvidas para amenizar o cenário pandêmico.
THE MULTIMODAL MANAGEMENT OF GROWTH HORMONE-SECRETING PITUITARY MACROADENOMA
Authors: Cazac Tabita Larisa
Published: March 2021

The expansive processes of the sellar region include tumors of mesenchymal, neural or epithelial origin, along with cystic and inflammatory processes. From the epithelial sellar tumors, almost 90 % are represented by pituitary adenomata – benign tumors which develop from the adenohypophyseal cells, accounting for approximately 10–15% of all intracranial expansive processes. According to the clinical criteria, the pituitary adenomata can be classified as endocrine-inactive or non-producing adenomata, and endocrine-active or producing adenomata. The non-producing adenomata represent approximately 39–50% of all pituitary tumors; the prolactinomata represent approximately 6.1%; the growth hormone producing adenomata approximately 27.9%; the adenocorticotropic hormone producing adenomata 6%; the thyrotropic producing hormone adenomata 0.4%; and the follicle-stimulating or luteinizing producing hormone adenomata are extremely rare. The surgical approach used on a large scale today in pituitary and suprasellar tumors is the transnasal transsphenoidal approach, which is less invasive compared to the standard transcranial approach and has got excellent results so far. The purpose of this article is to illustrate the main data about pituitary tumors, based on a case report presentation. At the same time, we aim to keep track of the latest information in the specialty literature, and focus on the neurosurgical aspects. The therapeutic strategy in the case of a 24-year-old female patient diagnosed with a growth hormone-secreting pituitary macroadenoma, with a suprasellar extension and an infrasellar one in the sphenoidal sinus and with invasion in the right cavernous sinus.
SURGICAL APPROACH OF HYPERTENSION: PHEOCHROMOCYTOMA CASE REPORT
Authors: Ion Adriana , Bostaca I.
Published: March 2021

Pheochromocytoma is present in about 1% of hypertensive patients. It has a 90% cure potential, but a high mortality rate if left untreated. Complications include malignant hypertension, heart failure, myocardial infarction, ventricular arrhythmias, stroke or metastasis (malignant pheochromocytoma). We present the case of a 47-year-old hypertensive female patient who was admitted to hospital in 2014 with excessive fluctuations in blood pressure (300/140 mmHg to 90/50 mmHg), rapid pulse not responding to medication, profuse night sweats, palpitations, vertigo, nausea, and vomiting. The patient had a history of high arterial pressure dating back to 1996, following complex anti-hypertensive treatment, and frequent episodes of paroxysmal atrial fibrillation in the previous four years, reduced by external electric shock. Laboratory and imaging investigations revealed a solid-type formation with mixed structure in the right adrenal gland, indicating pheochromocytoma. Surgery with resection of the right adrenal gland was proposed. Preoperative preparation to combat the risks of large variations in blood pressure and hypovolemia started 1–3 weeks before surgery, consisting of an alpha-blocker to control blood pressure, a beta-blocker to prevent arrhythmic events, and hydration to prevent postoperative hypotension. A right adrenalectomy was performed. Histopathology of the resected piece confirmed the diagnosis of pheochromocytoma. After surgery, the large variations in blood pressure, arrythmic events and tumor symptoms were all reduced, and blood pressure returned to within normal range. Follow-up treatment consisted of Carvedilol 12.5 mg, 1 cp / day and a low-salt, hypolipidaemic diet was recommended. The case is notable for the late diagnosis made about 18 years after the onset of the hypertensive symptoms, treated with excessive medication.
FROM VASOMOTOR SYMPTOMS TO SOLID AND INSULAR PAPILLARY THYROID CANCER WITH OXYPHIL VARIANT AREAS
Authors: Cașorte Mara , Albu Simona Elena , Iorgulescu R. , Dumitrașcu Anda , Terzea Dana , Golstein A. , Poiană Cătălina
Published: March 2021

The thyroid cancer had an increasing frequency during the last decades mostly related to better and accessible detection methods. The papillary type has the major epidemiologic impact. We present a case with mixed symptoms before surgery, a rare combination of both thyrotoxicosis and thyroid malignancy and an unusual pathologic report in a 56-year-old female known with total hysterectomy at age of 42, diagnosed with toxic goiter 2 years ago and under intermittent therapy with thiamazol. She presented for unspecific hot flashes and palpitation at gynaecology and she was referred for endocrine evaluation that revealed unspecific cervical compression complains, and a large goiter. The Thyroid-Stimulating Hormone was normal under thiamazol and so were the thyroid antibodies and calcitonin. The computed tomography pointed an isthmus and left lobe nodule of maximum 7.28 cm with mass effect on trachea. Total thyroidectomy was performed without any significant complications. The patient was hospitalised for 4 days (less than 48 hours postoperatively). The pathological report showed a papillary thyroid cancer (stage III) with oxyphil variant and an insular and solid pattern component. A high proliferative index is detected by vessels invasion and a ki-67 of 15 %. She received radioiodine therapy and then she started suppression levothyroxine treatment. The insular and oxyphilic pattern as well as the large tumour size of 6 cm suggest a severe prognosis. On the other hand, it is still a matter of debate whether non-autoimmune hyperthyroidism and solid pathologic features subscribe to the hypothesis of an aggressive cancer phenotype. Lifelong follow up is needed.
VESICOVAGINALS FISTULAS: THE EXPERIENCE OF OUR CLINIC ON SURGICAL TREATMENT AND RESULTS
Authors: Sima A. , Braticevici B. , Benguș F. , Petca R. , Jinga V.
Published: March 2021

Vesicovaginals fistulas are the most common type of urogenital fistulas resulting after radical hysterectomy with or without radiotherapy. In most cases, surgery is necessary for healing. The present study was conducted over a period of 5 years. In all cases, the diagnosis was made on medical history, a complete clinical examination, intravenous pyelography and cystoscopy. Surgical closing technique of fistula tract could be applied in 28 cases (68.29%), out of which in 9 (22%) patients the exicision of the fistula tract and separate suture of the bladder and the vagina were performed while in 19 ( 46.3%) patients a flap was interposed too. All 25 patients who presented fistula after radical hysterectomy were feasible to surgical treatment of demolition of fistula and only 3 of 16 (18.75%) of the cases of hysterectomy and radiotherapy had indication for surgical closing technique of fistula tract. In 4 cases (9.7%) an external urinary diversion as the only therapeutic solution was performed. In 3 cases (7.3%) a percutaneous nephrostomy was inserted. Two patients (4.8%) presented vesicovaginal fistula and rectovaginal fistula as well. 24 (85.71%) of the 28 cases that have benefited from surgery remained continent, without loss of urine vaginally after the removal of urethro-bladder catheter. In 13 (31.7%) cases the success could not be obtained due to radiotherapy associated with hysterectomy. In the 25 cases where radiotherapy was not enforced, the success rate of surgery was 92%, while in patients who have benefited from radiotherapy too it goes down drastically (33%).The surgical closing technique of the vesicovaginal fistula has a very high success rate. The success of the operation can be obtained from the first surgery. The associated radiotherapy has a big influence in the approach of this pathology surgery.
ADRENAL SURGICAL APPROACH IN A WOMAN WITH SYNCHRONOUS BILATERAL ADRENAL TUMORS
Authors: Albu Simona Elena , Cosorte Mara , Căpățînă Cristina , Dumitrașcu Anda , Ghemigian Adina
Published: March 2021

Bilateral adrenal tumours are very rare and display various endocrine profiles. The unilateralapproach is indicated if a nonsecretor contralateral pattern is suspected in order to avoid adrenal insufficiency.We present a 48-year-old woman with a history of bradimenorrhea at the age of 44.The gynecological evaluation was negative but two adrenal tumours were found. CT revealed aright adrenal tumour of 2 cm and a left one of 2.4 cm. Low-normal ACTH and high serumchromogranin A were confirmed. After one year, the left tumour increased to 4 cm so laparoscopictransabdominal left adrenalectomy (with 3 trocars) was successfully performed without anyincident. No conversion was required. Neither intraoperative nor postoperative complicationsoccurred. The patient was hospitalised 5 days and the wounds healed normally. The pathologicalreport revealed a benign corticoadenoma. The endocrine evaluation after one week showed thatafter surgery ACTH de-suppressed to normal and chromogranin A normalised. The right adrenaltumour was followed-up for another year and the diameters were stationary. The patient was stillhypertensive and she was offered adequate therapy (which we considered essential for high blood pressure). Life-long periodical check-up is necessary.Unilateral adrenalectomy in patients with both side tumours allows an adequate pathological report and avoids unnecessary contralateral surgery if an incidentaloma is revealed, thus allowing the preservation of adrenal function.
OUR EXPERIENCE IN THE SURGICAL MANAGEMENT OF PATIENTS WITH RECTAL NEOPLASTIC DISEASE
Authors: Tinca Alina Cristina , Palade R. , Ion D. , Nica Adriana Elena , Bolocan Alexandra , Ionescu Oana Adelina , Andronic O.
Published: March 2021

Colorectal cancer is one of the most commonly incriminated neoplastic pathologies and it has afairly high mortality rate. Although the therapeutic arsenal of rectal cancer has steadily improvedthrough the acquisition of biology, technology and pharmacology, the central role of surgicaltechnique is widely recognized in obtaining local control, on the one hand and a good quality of lifeof operated patient on the other hand. This article is a retrospective analysis of surgical proceduresfor rectal neoplasia conducted in order to determine to what extent technological development andcontinuous improvement of surgical techniques have influenced the evolution of patientmanagement with this pathology. This study was retrospective, observational, descriptive, single-center and it was held in the Department of General Surgery and Emergency III of the UniversityEmergency Hospital Bucharest during 1 January 2007 - March 31, 2016 and included a total of127 patients.
STRANGE CARDIAC COMPLICATION AFTER MEDIAN EVENTRATION SURGERY
Authors: Pătulea Roxana , Coțofană M. , Radu Georgiana , Păduraru D. N. , Andronic O. , Ion D.
Published: March 2021

A 51-year old patient comes to the hospital complaining of 20-30 bowel movements every day andabdominal pain following the introduction of a new medication for his cardiological problems(notable aspirin). His relevant medical history shows antecedents of hemorrhagic recto-colitis,non-stented coronaropathy, and a colectomy performed more than 10 years before. The diagnosiswas simple to make following laboratory, imagistic and clinical investigations – pouchitis andmedian eventrations following the prior surgery. The real problem appeared the next day followinghis eventration cure – cardiac tamponade in the context of antiplatelet medication. The patient wassuccessfully managed by the cardiothoracic surgeons. An intracardiac foreign body was found andeliminated during the intervention. Taking into consideration the fact that the patient had beentaking antiplatelet medication for almost a month, it is very likely that the foreign body hadmigrated there during or after the corrective surgical procedure for the eventration and created thehemopericardium in this particular context.
PARTICULARITIES OF DIAGNOSIS AND TREATMENT IN A CASE OF SYNCHRONOUS COLORECTAL CANCER
Authors: Mușat Florentina , Coțofană M. , Bolocan Alexandra , Andronic O. , Păduraru D. N.
Published: March 2021

In literature, synchronous colorectal cancer refers to the simultaneous presence of two or moremalignant lesions located along different segments of the large intestine or separated by at least 4cm, detected either pre-, intraoperatively or after maximum 6 months since a surgery addressed to acolon tumor. The incidence of synchronous tumors is approximately 3,5% of all cases of colorectalcarcinoma, while in others it reaches up to 8,4%. It is believed that this difference is mainly due tofalse negative results. The present paper presents the case of a 75-year-old patient, with a history ofessential hypertension and type 2 insulin-requiring diabetes who came to the emergency roomaccusing diffuse abdominal pain and bloating accompanied by the absence of intestinal transit forfecal matter over the past 6 days and an episode of vomiting. The results of the investigationscorrelated with the patient’s symptomatology indicate the diagnosis of bowel obstruction. Theexploratory laparotomy reveals an ulcero- vegetative, partially stenotic mass lesion in the sigmoidcolon with a diameter of about 5/6 cm. A second ulcero-vegetative, stenotic mass was identified atthe hepatic flexure of the colon with a diameter of approximately 8/7 cm. No metastatic lesions onthe liver or in the abdominal cavity were noted. Right hemicolectomy with end-to-endileotransverse-anastomosis and end-to-end colorectal anastomosis were performed. The presentpaper aims to expose the particular aspects of the diagnosis and treatment of bowel obstruction bysynchronous tumors on a patient with abdominal symptomatology attenuated on the background ofneurological complications of diabetes.
ENDOSCOPIC-ASSISTED ADENOIDECTOMY USING COBLATION. IS IT THE GOLD STANDARD?
Authors: Hainăroșie R. , Ștefănescu C. D. , Pantea Stoian Anca , Anghelina F. , Ioniță Irina Gabriela , Pietroșanu Cătălina , Rusescu Andreea , Iana Ruxandra Oana , Zainea V.
Published: March 2021

Adenoidectomy is one of the most common procedures, especially in the pediatric population. When accurately performed, it can cause significant changes in the quality of life of the patient, with minimum risks. Today, the surgeon has a large variety of surgical technologies available for this intervention, from the classical cold steel technique to the state of the art advancements, such as radiofrequency or coblation. The aim of this paper is to evaluate the advantages that are provided by coblation adenoidectomy, taking into account the duration of the intervention, the safety, and efficacy of the procedure and the postoperative pain. We consider all of these factors to be important, especially considering the difficult choice the surgeon faces in choosing the best technology for each patient.
LATE PRESENTING CONGENITAL DIAPHRAGMATIC HERNIA – A CASE SERIES
Authors: Datu R. C. , Stanciu Olivia , Enache T. , Andriescu M.
Published: March 2021

With an incidence of 1 to 2500 to 1 to 5000 births, congenital diaphragmatic hernia (CDH) can be a life-threatening condition. In 5-25% of the cases, CDH can present at older ages with non-specific signs and symptoms. The aim of our study was to assess the clinical aspects, the diagnosis and management of the patients with this affliction as well as increase the level of awareness on late-presenting CDH. Five patients older than 1 year of age at the moment of diagnosis of CDH were included in the study. The patients presented either for respiratory symptoms or gastrointestinal one. In all the cases, during initial assess, plain chest or abdominal x-rays were performed leading to the diagnosis of congenital diaphragmatic hernia. After further imaging studies (CT scans, ultrasound) all the patients underwent surgery for defect closure, 3 of them by the classic approach, 1 by laparoscopy and 1 by thoracoscopy. Three patients had left diaphragmatic defect and 2 had an anterior diaphragmatic defect. We extensively present the case of a 14-year-old female patient with a posterolateral diaphragmatic defect, in which gastric necrosis was found during surgery, leading to partial gastric resection and esogastric anastomosis. In this case, the postoperative evolution was critical and thepatient died in the 9th day postoperatively. The evolution of the other 4 patients was uneventful.
WHEN EVEN THE CLASSICS REQUIRE CLOSE SURVEILLANCE – A TYPICAL CASE OF MEN SYNDROME
Authors: Zaharia Irina , Mirică R. M. , Iosifescu R. , Dumitrașcu T. N. , Stănel Ioana Michaela , Mardare Mara , Spânu Andrada , Iordache N. , Ginghină O.
Published: March 2021

The genetic syndrome known in literature as the Multiple Endocrine Neoplasia type 1 (MEN 1) istransmitted in a dominant manner. The primary discovery of more than two endocrine tumorformations representative for MEN 1 should guide the doctor to the suspicion and subsequentconfirmation of the diagnosis. Statistics state a long association of the MEN 1 syndrome with thetumors discovered in the small intestine and the pancreas with the adenomas encountered in theparathyroid and pituitary glandular tissueWhile in postmenopausal women, the primaryhyperparathyroidism is diagnosed mostly with abnormal levels of parathyroid hormone and serumcalcium specifically. The most useful preoperative imaging tools are neck ultrasound scanning andtechnetium-99m sestamibi scintigraphy. Using bilateral neck exploration, subtotal, andparathyroidectomy are proposed. Our case consists of a 54 years old female, diagnosed with rightinferior parathyroid adenoma. With three first degree relatives operated for neuroendocrinepancreatic tumors, her medical history includes distal corporeal-caudal pancreatectomy for aneuroendocrine tumor four years ago. Laboratory tests unveil increased calcium (12, 41 mg/dl) andglucose (150 mg/dl) levels. During hospitalization, the patient’s representative parameters formonitoring hyperparathyroidism maintained at high levels. Parathyroid ultrasound and the 99mTctetrofosmin/99mTc-pertechnetate parathyroid scintigraphy sustained the diagnosis. Consequently,the patient was proposed for a subtotal parathyroidectomy with a pathology examination. It is highlyrecommended the interdisciplinary cooperation for the monitoring and management of patients withsuspicion of MEN 1. The annual assessment of serum calcium level, together with the parathyroidhormones, is proposed as a screening tool in early diagnosis.
SURGEON AND THE MACHINE – ROBOTS IN SURGERY
Authors: Ekci Baki , Agturk Gokhan
Published: March 2021

The use of tools and machines in the field of medicine is very old, although the use of robots datesback to several decades. The purpose of using machinery and robots in the industry is to reduceproduction costs in the industry. Unlike machines, robots are energy-driven mechanical systemsdesigned to perform learned operations and movements in a much safer faster and more economicalway. In the medical sector, robots used outside operations are used to automate certain tasks. Butthe surgical robots are controlled by the surgeons and used to facilitate the surgeons' work. In otherwords, they do not move except for the surgeon’s control and do not perform an automated procedureand they do not have artificial intelligence now. In this context, it is more appropriate to use the termrobotic-assisted surgical equipment, robot-assisted minimally invasive surgery or roboticallyassisted surgical devices rather than using the word “robot”. In short, robots used in surgeries aremachines designed to perform more complex, thinner, more precise tasks. In this review, we will beevaluating the robot, the different medical assistants and robotic surgery, the da Vinci robot, and thedifferences between the open surgery, laparoscopic surgery, and robot-assisted surgery.
THE PSYCHOLOGICAL IMPACT OF BREAST-CONSERVING SURGERY VERSUS MASTECTOMY IN EGYPTIAN FEMALE PATIENTS
Authors: Abdelatif Ahmed , Abounaggah Galal , Elmesery Mohamed , Asal Mohamed , Eweda Moataz
Published: March 2021

The previous research on breast cancer's psychological impact was based on its effects on shape, with breast removal, and the subsequent effect on sexual attractiveness. Several changes that affect life behavior after breast cancer surgery including insomnia, difficulty returning to usual activities and work, nightmares and loss of appetite. These manifestations may be due to depression but they are only considered abnormal if they persist after the period of physical recovery from surgery. We conducted a study to assess the effects of the surgical decision and psychological impact of this decision on Egyptian females with breast cancer. Most patients were subjected to a questionnaire including all environmental and clinical factors affecting the surgical decision either mastectomy or breast-conserving surgery. As a conclusion we can say that breast conservative surgery is better accepted psychologically by patients than modified radical mastectomy as it did not affect sexual life, cosmetic appearance, mood, self-satisfaction, and quality of life.
HEPATIC HYDATID CYST RUPTURED INTRABILIARY IN A 28-YEAR-OLD HIV POSITIVE PATIENT
Authors: Păduraru Dan Nicolae , Radu Georgiana , Tinca Alina , Ion Daniel , Smarandache Bianca , Oprea Erika , Constantinescu Gabriel , Andronic Octavian
Published: March 2021

Echinococcosis is an endemic disease in countries from the Mediterranean area, Eastern Europe, the Middle and the Far East, Australia, South America and Eastern Africa. However, it has a worldwide distribution because the dog, a definitive host, is a ubiquitous animal. Another important factor that led to a worldwide spread of the disease is population migration, as the number of cases in non-endemic regions has been increasing. We present the case of a 28-year-old HIV positive patient suffering from a liver hydatid cyst that had ruptured inside the biliary pathways. US and CT were the imaging tools used to establish a preoperatory diagnosis and the main therapeutic approach was neutralizing the parasite using 90 degrees alcohol, Lagot deroofing, contents’ evacuation through open surgery and appropriate drainage afterward. ERCP was very useful in unblocking the main biliary pathways after the surgery as well as installing a stent to ensure its further permeability.
AFIKSASI (PREFIKS DAN SUFIKS) DALAM KOLOM EKONOMI BISNIS DI KORAN JAWA POS EDISI KAMIS 14 NOVEMBER 2019
Authors: Jannah Miftachul
Published: March 2021

Penulisan penelitian ini bertujuan untuk memaparkan penjelasan Afiksasiyakni prefiks dan sufiks dalam kolom Ekonomi Bisnis di Jawa Pos Edisi Kamis 14November 2019 sebagai media dalam pelaksanaan jurnal penelitian afiksasi yangmeliputi prefiks dan sufiks. Penelitian ini untuk memudahkan cara membedakanafiksasi yakni prefiks dan sufiks dalam Bahasa Indonesia.Di dalam morfologi terdapatproses morfemis salah satunya yakni afiksasi. Afiksasi sendiri ialah suatu prosespembentukan pada kata yang mengalami pengimbuhan atau pembubuhan afiks padasebuah kata dasar ataupun bentuk dasar. baik itu dari kata dasar tunggal ataupunkompleks. Di dalam proses afiksasi kita akan menemui prefiks, infiks, sufiks, konfiks,dan simulfiks. Dari pembahasan diatas berkenan dengan analisis afiksasi (prefiks dansufiks) pada kolom ekonomi bisnis di jawa pos edisi 14 november 2019 didapatkanhasil bahwa proses afiksasi khususnya prefiks dan sufiks.Prefiks ialah sebuah afiksyang pengimbuhannya diletakkan pada bagian awal dari sebuah kata dasar ataubentuk dasar. Sedangkan pada proses pengimbuhan itu sendiri biasa kita jugamengenali prefiksasi. Sedangkan sufiks ialah sebuah afiks yang diimbuhkan padabagian belakang dari kata dasar atau bentuk dasar. Sedangkan pada prosespengimbuhan itu sendiri biasa kita juga mengenali sufiksasi. Apabila kita membahasproses afiksasi, di dalamnya pasti sedikit membahas kata dasar pula dan bentuk dasar.Kata dasar ialah kata yang belum memiliki perubahan, belum mengalami perubahanatau proses morfologis, entah itu semacam proses penambahan imbuhan, prosespengulangan ataupun proses pemajemukan. Bentuk dasar ialah bentuk yang menjadidasar di dalam proses morfologis, bisa bermacam kata dasar, kata imbuhan, kataulang, dan dapat pula kata majemuk.
NARRATIVE RESEARCH; A RESEARCH DESIGN
Authors: Afan Faizin
Published: March 2021

The word narrative describes or describes something in a detailed and chronological story. The procedure in narrative research requires the researcher to get the full story of or from the individual who is the subject of one's research. After obtaining data about someone who is the subject of complete knowledge, researchers must describe the data in a narrative. The analysis used in narrative research includes the strategies used by researchers in describing the story chronologically and completely, studies in biographies that portray all life forms of the study subject
Identifying and Engineering Bottlenecks of Autotrophic Isobutanol Formation in Recombinant C. ljungdahlii by Systemic Analysis
Authors: Hermann Maria , Teleki Attila , Weitz Sandra , Niess Alexander , Freund Andreas , Bengelsdorf Frank Robert , Dürre Peter , Takors Ralf
Published: March 2021

Clostridium ljungdahlii(C. ljungdahlii, CLJU) is natively endowed producing acetic acid, 2,3-butandiol, and ethanol consuming gas mixtures of CO2, CO, and H2(syngas). Here, we present the syngas-based isobutanol formation usingC. ljungdahliiharboring the recombinant amplification of the “Ehrlich” pathway that converts intracellular KIV to isobutanol. Autotrophic isobutanol production was studied analyzing two different strains in 3-L gassed and stirred bioreactors. Physiological characterization was thoroughly applied together with metabolic profiling and flux balance analysis. Thereof, KIV and pyruvate supply were identified as key “bottlenecking” precursors limiting preliminary isobutanol formation in CLJU[KAIA] to 0.02 g L–1. Additional blocking of valine synthesis in CLJU[KAIA]:ilvEincreased isobutanol production by factor 6.5 finally reaching 0.13 g L–1. Future metabolic engineering should focus on debottlenecking NADPH availability, whereas NADH supply is already equilibrated in the current generation of strains.
10-Gingerol Suppresses Osteoclastogenesis in RAW264.7 Cells and Zebrafish Osteoporotic Scales
Authors: Zang Liqing , Kagotani Kazuhiro , Nakayama Hiroko , Bhagat Jacky , Fujimoto Yuki , Hayashi Akihito , Sono Ryoji , Katsuzaki Hirotaka , Nishimura Norihiro , Shimada Yasuhito
Published: March 2021

Osteoporosis is the most common aging-associated bone disease and is caused by hyperactivation of osteoclastic activity. We previously reported that the hexane extract of ginger rhizome [ginger hexane extract (GHE)] could suppress receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells. However, the anti-osteoclastic components in GHE have not yet been identified. In this study, we separated GHE into several fractions using silica gel column chromatography and evaluated their effects on osteoclastogenesis using a RAW264.7 cell osteoclast differentiation assay (in vitro) and the zebrafish scale model of osteoporosis (in vivo). We identified that the fractions containing 10-gingerol suppressed osteoclastogenesis in RAW264.7 cells detected by tartrate-resistant acid phosphatase (TRAP) staining. In zebrafish, GHE and 10-gingerol suppressed osteoclastogenesis in prednisolone-induced osteoporosis regenerated scales to promote normal regeneration. Gene expression analysis revealed that 10-gingerol suppressed osteoclast markers in RAW264.7 cells [osteoclast-associated immunoglobulin-like receptor, dendrocyte-expressed seven transmembrane protein, and matrix metallopeptidase-9 (Mmp9)] and zebrafish scales [osteoclast-specific cathepsin K (CTSK), mmp2, and mmp9]. Interestingly, nuclear factor of activated T-cells cytoplasmic 1, a master transcription regulator of osteoclast differentiation upstream of the osteoclastic activators, was downregulated in zebrafish scales but showed no alteration in RAW264.7 cells. In addition, 10-gingerol inhibited CTSK activity under cell-free conditions. This is the first study, to our knowledge, that has found that 10-gingerol in GHE could suppress osteoclastic activity in both in vitro and in vivo conditions.
Mechanism and Control of Meiotic DNA Double-Strand Break Formation in S. cerevisiae
Authors: Yadav Vikash Kumar , Claeys Bouuaert Corentin
Published: March 2021

Developmentally programmed formation of DNA double-strand breaks (DSBs) by Spo11 initiates a recombination mechanism that promotes synapsis and the subsequent segregation of homologous chromosomes during meiosis. Although DSBs are induced to high levels in meiosis, their formation and repair are tightly regulated to minimize potentially dangerous consequences for genomic integrity. InS. cerevisiae, nine proteins participate with Spo11 in DSB formation, but their molecular functions have been challenging to define. Here, we describe our current view of the mechanism of meiotic DSB formation based on recent advances in the characterization of the structure and function of DSB proteins and discuss regulatory pathways in the light of recent models.
Prediction of Sepsis in COVID-19 Using Laboratory Indicators
Authors: Tang Guoxing , Luo Ying , Lu Feng , Li Wei , Liu Xiongcheng , Nan Yucen , Ren Yufei , Liao Xiaofei , Wu Song , Jin Hai , Zomaya Albert Y. , Sun Ziyong
Published: March 2021

Background

The outbreak of coronavirus disease 2019 (COVID-19) has become a global public health concern. Many inpatients with COVID-19 have shown clinical symptoms related to sepsis, which will aggravate the deterioration of patients’ condition. We aim to diagnose Viral Sepsis Caused by SARS-CoV-2 by analyzing laboratory test data of patients with COVID-19 and establish an early predictive model for sepsis risk among patients with COVID-19.

Methods

This study retrospectively investigated laboratory test data of 2,453 patients with COVID-19 from electronic health records. Extreme gradient boosting (XGBoost) was employed to build four models with different feature subsets of a total of 69 collected indicators. Meanwhile, the explainable Shapley Additive ePlanation (SHAP) method was adopted to interpret predictive results and to analyze the feature importance of risk factors.

Findings

The model for classifying COVID-19 viral sepsis with seven coagulation function indicators achieved the area under the receiver operating characteristic curve (AUC) 0.9213 (95% CI, 89.94–94.31%), sensitivity 97.17% (95% CI, 94.97–98.46%), and specificity 82.05% (95% CI, 77.24–86.06%). The model for identifying COVID-19 coagulation disorders with eight features provided an average of 3.68 (±) 4.60 days in advance for early warning prediction with 0.9298 AUC (95% CI, 86.91–99.04%), 82.22% sensitivity (95% CI, 67.41–91.49%), and 84.00% specificity (95% CI, 63.08–94.75%).

Interpretation

We found that an abnormality of the coagulation function was related to the occurrence of sepsis and the other routine laboratory test represented by inflammatory factors had a moderate predictive value on coagulopathy, which indicated that early warning of sepsis in COVID-19 patients could be achieved by our established model to improve the patient’s prognosis and to reduce mortality.
A Comprehensive Analysis of Genomics and Metagenomics in a Heterozygote Familial Hypercholesterolemia Family
Authors: Liu Honghong , Jin Ye , Tian Ran , Feng Siqin , Zhang Shuyang , Zhang Chenhong
Published: March 2021

Familial hypercholesterolemia (FH) is an inherited rare disease leading to markedly elevated low-density lipoprotein cholesterol (LDL-C) levels and increased risk for cardiovascular event. Gut microbiota has been implicated as a pivotal contributing factor in hyperlipidemia, however, its role in FH remains elusive. We performed whole-exome and metagenomics sequencing on a family with 22 members in which myocardial infarctions occurred at a young age with unclear etiology. We confirmed the missense mutation of LDLR c.1723C>T accounted for the abnormal cholesterol metabolism in the family through co-segregation analysis. In addition, Prevotella dentalis was found elevated and strongly associated with LDL-C level in FH family members with mutation of LDLR c.1723C>T compared to unaffected members with hyperlipidemia. Overall, our work suggests that whole-exome sequencing can facilitate identification of disease-causing variants and enable preventive treatment of FH. Our metagenomics analysis provides early insights into potential contributions of host-microbe interactions in genetic and common hypercholesterolemia.
Application of Subspace-Based Detection Algorithm to Infrasound Signals in Volcanic Areas
Authors: Sciotto Mariangela , Montalto Placido
Published: March 2021

Infrasonic signals investigation plays a fundamental role for both volcano monitoring purpose and the study of the explosion dynamics. Proper and reliable detection of weak signals is a critical issue in active volcano monitoring. In particular, in volcanic acoustics, it has direct consequences in pinpointing the real number of generated events (amplitude transients), especially when they exhibit low amplitude, are close in time to each other, and/or multiple sources exist. To accomplish this task, several algorithms have been proposed in literature; in particular, to overcome limitations of classical approaches such as short-time average/long-time average and cross-correlation detector, in this paper a subspace-based detection technique has been implemented. Results obtained by applying subspace detector on real infrasound data highlight that this method allows sensitive detection of lower energy events. This method is based on a projection of a sliding window of signal buffer onto a signal subspace that spans a collection of reference signals, representing similar waveforms from a particular infrasound source. A critical point is related to subspace design. Here, an empirical procedure has been applied to build the signal subspace from a set of reference waveforms (templates). In addition, in order to determine detectors parameters, such as subspace dimension and detection threshold, even in presence of overlapped noise such as infrasonic tremor, a statistical analysis of noise has been carried out. Finally, the subspace detector reliability and performance, have been assessed by performing a comparison among subspace approach, cross-correlation detector and short-time average/long-time average detector. The obtained confusion matrix and extrapolated performance indices have demonstrated the potentiality, the advantages and drawbacks of the subspace method in tracking volcanic activity producing infrasound events. This method revealed to be a good compromise in detecting low-energy and very close in time events recorded during Strombolian activity.
Exploration of a Robust and Prognostic Immune Related Gene Signature for Cervical Squamous Cell Carcinoma
Authors: Zuo Zhihua , Xiong Junjun , Zeng Chuyi , Jiang Yao , Xiong Kang , Tao Hualin , Guo Yongcan
Published: March 2021

Background: Cervical squamous cell carcinoma (CESC) is one of the most frequent malignancies in women worldwide. The level of immune cell infiltration and immune-related genes (IRGs) can significantly affect the prognosis and immunotherapy of CESC patients. Thus, this study aimed to identify an immune-related prognostic signature for CESC.

Methods: TCGA-CESC cohorts, obtained from TCGA database, were divided into the training group and testing group; while GSE44001 dataset from GEO database was viewed as external validation group. ESTIMATE algorithm was applied to evaluate the infiltration levels of immune cells of CESC patients. IRGs were screened out through weighted gene co-expression network analysis (WGCNA). A multi-gene prognostic signature based on IRGs was constructed using LASSO penalized Cox proportional hazards regression, which was validated through Kaplan–Meier, Cox, and receiver operating characteristic curve (ROC) analyses. The abundance of immune cells was calculated using ssGSEA algorithm in the ImmuCellAI database, and the response to immunotherapy was evaluated using immunophenoscore (IPS) analysis and the TIDE algorithm.

Results: In TCGA-CESC cohorts, higher levels of immune cell infiltration were closely associated with better prognoses. Moreover, a prognostic signature was constructed using three IRGs. Based on this given signature, Kaplan–Meier analysis suggested the significant differences in overall survival (OS) and the ROC analysis demonstrated its robust predictive potential for CESC prognosis, further confirmed by internal and external validation. Additionally, multivariate Cox analysis revealed that the three IRGs signature served as an independent prognostic factor for CESC. In the three-IRGs signature low-risk group, the infiltrating immune cells (B cells, CD4/8 + T cells, cytotoxic T cells, macrophages and so on) were much more abundant than that in high-risk group. Ultimately, IPS and TIDE analyses showed that low-risk CESC patients appeared to present with a better response to immunotherapy and a better prognosis than high-risk patients.

Conclusion: The present prognostic signature based on three IRGs (CD3E, CD3D, LCK) was not only reliable for survival prediction but efficient to predict the clinical response to immunotherapy for CESC patients, which might assist in guiding more precise individual treatment in the future.
The Cologne Picture Naming Test for Language Mapping and Monitoring (CoNaT): An Open Set of 100 Black and White Object Drawings
Authors: Weiss Lucas Carolin , Pieczewski Julia , Kochs Sophia , Nettekoven Charlotte , Grefkes Christian , Goldbrunner Roland , Jonas Kristina
Published: March 2021

Language assessment using a picture naming task crucially relies on the interpretation of the given verbal response by the rater. To avoid misinterpretations, a language-specific and linguistically controlled set of unambiguous, clearly identifiable and common object–word pairs is mandatory. We, here, set out to provide an open-source set of black and white object drawings, particularly suited for language mapping and monitoring, e.g., during awake brain tumour surgery or transcranial magnetic stimulation, in German language. A refined set of 100 black and white drawings was tested in two consecutive runs of randomised picture order and was analysed in respect of correct, prompt, and reliable object recognition and naming in a series of 132 healthy subjects between 18 and 84 years (median 25 years, 64% females) and a clinical pilot cohort of 10 brain tumour patients (median age 47 years, 80% males). The influence of important word- and subject-related factors on task performance and reliability was investigated. Overall, across both healthy subjects and patients, excellent correct object naming rates (97 vs. 96%) as well as high reliability coefficients (Goodman–Kruskal's gamma = 0.95 vs. 0.86) were found. However, the analysis of variance revealed a significant, overall negative effect of low word frequency (p < 0.05) and high age (p < 0.0001) on task performance whereas the effect of a low educational level was only evident for the subgroup of 72 or more years of age (p < 0.05). Moreover, a small learning effect was observed across the two runs of the test (p < 0.001). In summary, this study provides an overall robust and reliable picture naming tool, optimised for the clinical use to map and monitor language functions in patients. However, individual familiarisation before the clinical use remains advisable, especially for subjects that are comparatively prone to spontaneous picture naming errors such as older subjects of low educational level and patients with clinically apparent word finding difficulties.
Measuring Wasting and Stunting Prevalence Among Children Under 5 Years of Age and Associated Risk Factors in Papua New Guinea: New Evidence From the Comprehensive Health and Epidemiological Surveillance System
Authors: Pham Bang Nguyen , Silas Vinson D. , Okely Anthony D. , Pomat William
Published: March 2021

Background: Papua New Guinea (PNG) has undergone a significant health transition, with the prevalence of non-communicable diseases increasing. Many children under 5 years of age suffer from the burden of malnutrition. While wasting and stunting still remain high, children who are overweight and obese are reportedly increasing.

Objective: This study reports the prevalence of wasting, stunting, underweight, and overweight children under five in PNG and explores potential household and maternal socioeconomic factors associated with malnutrition.

Method: Data were drawn from the Comprehensive Health and Epidemiological Surveillance System (CHESS) in PNG. Height and weight were directly measured, and wasting, stunting, overweight, and underweight statistics were determined using the 2006 WHO Standard Growth Standards. Household and maternal factors were assessed with parent interviews conducted by trained data collectors. Multivariate logistic regression analyses were conducted to report associations between selected socioeconomic correlates and child malnutrition outcomes.

Result: The prevalence of wasting, stunting, underweight, and overweight children was 13.8, 46.5, 18.2, and 18%, respectively. Children from households with food shortage were more likely to be wasted than those from households without such an experience [OR: 1.43 (95% CI: 0.93–2.21)]. Children from the poor quintile were more likely to be stunted than those from the richest quintile [OR: 1.2 (95% CI: 0.79–1.82)]. Other factors associated with wasting included living in an urban vs. rural area [OR: 1.36 (0.77–2.4)], middle household wealth quintile vs. richest quintile [OR: 0.77 (0.38–1.55)], mothers in union with a man vs. mother unmarried or live in union [OR: 0.76 (0.4–1.42)], and male children vs. female [OR: 0.77 (0.53–1.11)]. Factors associated with stunting included residing in urban vs. rural areas [OR: 1.13 (0.8–1.6)], mother in union vs. single mother [OR: 0.86 (0.59–1.24)], and mothers with preparatory/elementary vs. mothers with vocational/college education [OR: 0.15 (0.02–1.01)].

Conclusion: An integrated approach is needed to comprehensively address the household socioeconomic factors at the household level, contributing to the improvement of child health and development in PNG.
Genomic Profiling Identified Novel Prognostic Biomarkers in Chinese Midline Glioma Patients
Authors: Li Hainan , Shan Changguo , Wu Shengnan , Cheng Baijie , Fan Chongzu , Cai Linbo , Chen Yedan , Shi Yuqian , Liu Kaihua , Shao Yang , Zhu Dan , Li Zhi
Published: March 2021

Background

Molecular characteristics are essential for the classification and grading of gliomas. However, diagnostic classification of midline glioma is still debatable and substantial molecular and clinical heterogeneity within each subgroup suggested that they should be further stratified. Here, we studied the mutation landscape of Chinese midline glioma patients in hope to provide new insights for glioma prognosis and treatment.

Methods

Tissue samples from 112 midline glioma patients underwent next-generation sequencing targeting 425 cancer-relevant genes. Gene mutations and copy number variations were investigated for their somatic interactions and prognostic effect using overall survival data. Pathway-based survival analysis was performed for ten canonical oncogenic pathways.

Results

We identified several currently established diagnostic and prognostic biomarkers of glioma, including TP53 (33%), EGFR (26%), TERT (24%), PTEN (21%), PIK3CA (14%), ATRX (14%), BRAF (13%), and IDH1/2 (6%). Among all genetic aberrations with more than 5% occurrence rate, six mutations and three copy number gains were greatly associated with poor overall survival (univariate, P < 0.1). Of these, TERT mutations (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.37–6.61; P = 0.01) and PIK3CA mutations (HR, 2.04; 95% CI, 1.08–3.84; P = 0.02) remained significant in multivariate analyses. Additionally, we have also identified a novel MCL1 amplification (found in 31% patients) as a potential independent biomarker for glioma (multivariate HR, 2.78; 95% CI, 1.53–5.08; P < 0.001), which was seldom reported in public databases. Pathway analyses revealed significantly worse prognosis with abnormal PI3K (HR, 1.81; 95% CI, 1.12–2.95; P = 0.01) and cell cycle pathways (HR, 1.97; 95% CI, 1.15–3.37; P = 0.01), both of which stayed meaningful after multivariate adjustment.

Conclusions

In this study, we discovered shorter survival in midline glioma patients with PIK3CA and TERT mutations and with abnormal PI3K and cell cycle pathways. We also revealed a novel prognostic marker, MCL1 amplification that collectively provided new insights and opportunities in understanding and treating midline gliomas.