bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility and first results of a prospective cohort study to investigate cisplatin-associated ototoxicity amongst cancer patients in South Africa
Authors: Paken Jessica , Govender Cyril D. , Pillay Mershen , Ayele Birhanu T. , Sewram Vikash
Published: July 2021

Background

Cervical cancer, one of the most common cancers affecting females in South Africa, commonly requires a cisplatin-based-treatment regimen, which has been associated with ototoxic side effects. However, cisplatin-associated ototoxicity is largely under-reported in South Africa, despite its impact of hearing loss having serious overt ramifications on the quality of life of these patients. Hence, a prospective cohort study was undertaken to assess the audiological changes in female cervical cancer patients receiving cisplatin therapy.

Objective

To present details of the feasibility study and initial results on hearing patterns in cervical cancer patients receiving cisplatin chemotherapy. .

Methods

Fifty cervical cancer patients commencing with cisplatin chemotherapy underwent audiological assessments at a hospital in South Africa at various time intervals. Assessments included case history, otoscopic examination, immittance audiometry, pure tone audiometry (including high-frequency audiometry), speech audiometry, and distortion product otoacoustic emission testing. Data analysis involved the use of descriptive statistics and the Cochran-Armitage trend test for a linear trend in proportions.

Results

Fifty participants, aged between 32 and 79 years (Mean: 53 years; SD = 11.00), were recruited. Clinical findings revealed an incidence of 100% ototoxic hearing loss at the one-month post-treatment, i.e., 98%  after three cycles of cisplatin and 2%  at one-month post-chemotherapy. Sensorineural hearing loss and high-frequency tinnitus were most common. Deterioration in hearing thresholds was more evident in the extended high-frequency range, with the number of “no-responses,” from 11,200 Hz to 20,000 Hz, increasing with each successive audiological evaluation. This study further indicated that recruitment and follow-up of study participants within a limited resource setting are possible. However, cognizance must be given to a multidisciplinary approach and constant engagement with participants through regular contact either telephonically or via a short-message-system.

Conclusion

Exposure to cisplatin treatment contributed to hearing loss in females with cervical cancer, highlighting the need for ototoxicity monitoring during chemotherapy treatments. Furthermore, the results indicate that it is possible to conduct prospective cohort studies, using a multidisciplinary approach in limited-resource environments with appropriate planning and training strategies, as this study was able to achieve its aim successfully.
Use of antithrombotics at the end of life: an in-depth chart review study
Authors: Huisman Bregje A.A. , Geijteman Eric C.T. , Arevalo Jimmy J. , Dees Marianne K. , van Zuylen Lia , Szadek Karolina M. , van der Heide Agnes , Steegers Monique A.H.
Published: July 2021

Background

Antithrombotics are frequently prescribed for patients with a limited life expectancy. In the last phase of life, when treatment is primarily focused on optimizing patients’ quality of life, the use of antithrombotics should be reconsidered.

Methods

We performed a secondary analysis of a retrospective review of 180 medical records of patients who had died of a malignant or non-malignant disease, at home, in a hospice or in a hospital, in the Netherlands. All medication prescriptions and clinical notes of patients using antithrombotics in the last three months of life were reviewed manually. We subsequently developed case vignettes based on a purposive sample, with variation in setting, age, gender, type of medication, and underlying disease.

Results

In total 60% (n=108) of patients had used antithrombotics in the last three months of life. Of all patients using antithrombotics 33.3 % died at home, 21.3 % in a hospice and 45.4 % in a hospital. In total, 157 antithrombotic prescriptions were registered; 30 prescriptions of vitamin K antagonists, 60 of heparins, and 66 of platelet aggregation inhibitors. Of 51 patients using heparins, 32 only received a prophylactic dose. In 75.9 % of patients antithrombotics were continued until the last week before death. Case vignettes suggest that inability to swallow, bleeding complications or the dying phase were important factors in making decisions about the use of antithrombotics.

Conclusions

Antithrombotics in patients with a life limiting disease are often continued until shortly before death. Clinical guidance may support physicians to reconsider (dis)continuation of antithrombotics and discuss this with the patient.
Effectiveness of iguratimod as monotherapy or combined therapy in patients with rheumatoid arthritis: a systematic review and meta-analysis of RCTs
Authors: Hu Chao-Jun , Zhang Li , Zhou Shuang , Jiang Nan , Zhao Jiu-Liang , Wang Qian , Tian Xin-Ping , Zeng Xiao-Feng
Published: July 2021

Background

This study aims to evaluate the efficacy and safety of the iguratimod (IGU) as monotherapy or combined therapy in patients with rheumatoid arthritis (RA) by using meta-analysis.

Methods

We searched Medline, EMBASE, Cochrane library, CNKI, Wanfang medical network from initial to 30 June, 2020, for randomized clinical trials (RCTs). Two authors independently screened the studies via reading the title, abstract, and full text. The risk of bias in individual studies was assessed using the Cochrane Risk of Bias tool. STATA 12.0 was used for pooled analysis of all included studies.

Results

A total of 23 RCTs were included in this analysis. Meta-analysis showed that patients in the IGU monotherapy or combined therapy group had significantly higher ACR20 (OR = 1.97, 95% CI 1.29 to 3.00,P= 0.002), lower DAS28-CRP (SMD = −3.49, 95% CI −5.40 to −1.58,P< 0.001) and DAS28-ESR (SMD = −2.61, 95% CI −3.64 to −1.57,P< 0.001), as well as shorter duration of morning stiffness (SMD = −2.06, 95% CI −2.86 to −1.25,P< 0.001) and lower HAQ score (SMD = −0.91, 95% CI −1.61 to −0.21,P= 0.011), than those received other disease-modifying antirheumatic drugs (DMARDs) monotherapy (primarily comprising methotrexate). For the safety profile, IGU monotherapy had similar risks for gastrointestinal reactions (P= 0.070), leucopenia (P= 0.309), increment in transaminase (P= 0.321), increase of ALT (P= 0.051), and liver damage (P= 0.182) to methotrexate monotherapy, and IGU combined with other DMARDs therapy did not increase the risks of these AEs (P> 0.05).

Conclusions

Our evidence suggests that IGU is effective and tolerant as monotherapy or combined therapy especially with methotrexate in patients with active RA. IGU may be regarded as a potential alternative to methotrexate, and a preferable choice when combined with other DMARDs for the treatment of RA.
Personalized mechanical ventilation in acute respiratory distress syndrome
Authors: Pelosi Paolo , Ball Lorenzo , Barbas Carmen S. V. , Bellomo Rinaldo , Burns Karen E. A. , Einav Sharon , Gattinoni Luciano , Laffey John G. , Marini John J. , Myatra Sheila N. , Schultz Marcus J. , Teboul Jean Louis , Rocco Patricia R. M.
Published: July 2021

A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume (VT) is a standard of care, further individualization of VT may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust VT and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.
Secondary resistance to anti-EGFR therapy by transcriptional reprogramming in patient-derived colorectal cancer models
Authors: Vangala Deepak , Ladigan Swetlana , Liffers Sven T. , Noseir Soha , Maghnouj Abdelouahid , Götze Tina-Maria , Verdoodt Berlinda , Klein-Scory Susanne , Godfrey Laura , Zowada Martina K. , Huerta Mario , Edelstein Daniel L. , de Villarreal Jaime Martinez , Marqués Miriam , Kumbrink Jörg , Jung Andreas , Schiergens Tobias , Werner Jens , Heinemann Volker , Stintzing Sebastian , Lindoerfer Doris , Mansmann Ulrich , Pohl Michael , Teschendorf Christian , Bernhardt Christiane , Wolters Heiner , Stern Josef , Usta Selami , Viebahn Richard , Admard Jacob , Casadei Nicolas , Fröhling Stefan , Ball Claudia R. , Siveke Jens T. , Glimm Hanno , Tannapfel Andrea , Schmiegel Wolff , Hahn Stephan A.
Published: July 2021

Background

The development of secondary resistance (SR) in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (anti-EGFR) antibodies is not fully understood at the molecular level. Here we tested in vivo selection of anti-EGFR SR tumors in CRC patient-derived xenograft (PDX) models as a strategy for a molecular dissection of SR mechanisms.

Methods

We analyzed 21 KRAS, NRAS, BRAF, and PI3K wildtype CRC patient-derived xenograft (PDX) models for their anti-EGFR sensitivity. Furthermore, 31 anti-EGFR SR tumors were generated via chronic in vivo treatment with cetuximab. A multi-omics approach was employed to address molecular primary and secondary resistance mechanisms. Gene set enrichment analyses were used to uncover SR pathways. Targeted therapy of SR PDX models was applied to validate selected SR pathways.

Results

In vivo anti-EGFR SR could be established with high efficiency. Chronic anti-EGFR treatment of CRC PDX tumors induced parallel evolution of multiple resistant lesions with independent molecular SR mechanisms. Mutations in driver genes explained SR development in a subgroup of CRC PDX models, only. Transcriptional reprogramming inducing anti-EGFR SR was discovered as a common mechanism in CRC PDX models frequently leading to RAS signaling pathway activation. We identified cAMP and STAT3 signaling activation, as well as paracrine and autocrine signaling via growth factors as novel anti-EGFR secondary resistance mechanisms. Secondary resistant xenograft tumors could successfully be treated by addressing identified transcriptional changes by tailored targeted therapies.

Conclusions

Our study demonstrates that SR PDX tumors provide a unique platform to study molecular SR mechanisms and allow testing of multiple treatments for efficient targeting of SR mechanisms, not possible in the patient. Importantly, it suggests that the development of anti-EGFR tolerant cells via transcriptional reprogramming as a cause of anti-EGFR SR in CRC is likely more prevalent than previously anticipated. It emphasizes the need for analyses of SR tumor tissues at a multi-omics level for a comprehensive molecular understanding of anti-EGFR SR in CRC.
RETRACTED ARTICLE: Mesenchymal stem cells ameliorate renal fibrosis by galectin-3/Akt/GSK3β/Snail signaling pathway in adenine-induced nephropathy rat
Authors: Tang Huajun , Zhang Peiyue , Zeng Lianlin , Zhao Yu , Xie Libo , Chen Bo
Published: July 2021

Background

Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics.

Methods

TIF model was induced by adenine gavage. Bone marrow-derived MSCs was injected by tail vein after modeling. Renal function and fibrosis related parameters were assessed by Masson, Sirius red, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry. Further possible mechanism was explored by transfected galectin-3 gene for knockdown (Gal-3 KD) and overexpression (Gal-3 OE) in HK-2 cells with lentiviral vector.

Results

MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-β1, Kim-1, p-Smad2/3, IL-6, IL-1β, and TNFα compared with model rats, while p38 MAPK increased. Proteomics showed that only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared MSCs group with the model group. Galectin-3 was downregulated significantly in renal tissues and TGF-β1-induced rat tubular epithelial cells and interstitial fibroblasts, consistent with the iTRAQ results. Gal-3 KD notably inhibited the expression of p-Akt, p-GSK3β and snail in TGF-β1-induced HK-2 cells fibrosis. On the contrary, Gal-3 OE obviously increased the expression of p-Akt, p-GSK3β and snail.

Conclusion

The mechanism of MSCs anti-renal fibrosis was probably mediated by galectin-3/Akt/GSK3β/Snail signaling pathway. Galectin-3 may be a valuable target for treating renal fibrosis.
Assessment of changes in autophagic vesicles in human immune cell lines exposed to nano particles
Authors: David Christopher A. W. , del Castillo Busto M. Estela , Cuello-Nuñez Susana , Goenaga-Infante Heidi , Barrow Michael , Fernig David G. , Murray Patricia , Rosseinsky Matthew J. , Owen Andrew , Liptrott Neill J.
Published: July 2021

Background

Safe and rational development of nanomaterials for clinical translation requires the assessment of potential biocompatibility. Autophagy, a critical homeostatic pathway intrinsically linked to cellular health and inflammation, has been shown to be affected by nanomaterials. It is, therefore, important to be able to assess possible interactions of nanomaterials with autophagic processes.

Results

CEM (T cell), Raji (B lymphocyte), and THP-1 (human monocyte) cell lines were subject to treatment with rapamycin and chloroquine, known to affect the autophagic process, in order to evaluate cell line-specific responses. Flow cytometric quantification of a fluorescent autophagic vacuole stain showed that maximum observable effects (105%, 446%, and 149% of negative controls) were achieved at different exposure durations (8, 6, and 24 h for CEM, Raji, and THP-1, respectively). THP-1 was subsequently utilised as a model to assess the autophagic impact of a small library of nanomaterials. Association was observed between hydrodynamic size and autophagic impact (r2 = 0.11, p = 0.004). An ELISA for p62 confirmed the greatest impact by 10 nm silver nanoparticles, abolishing p62, with 50 nm silica and 180 nm polystyrene also lowering p62 to a significant degree (50%, 74%, and 55%, respectively, p < 0.05).

Conclusions

This data further supports the potential for a variety of nanomaterials to interfere with autophagic processes which, in turn, may result in altered cellular function and viability. The association of particle size with impact on autophagy now warrants further investigation.

Graphic abstract
New criteria for selecting reliable Thellier-type paleointensity results from the 1960 Kilauea lava flows, Hawaii
Authors: Jeong Doohee , Liu Qingsong , Yamamoto Yuhji , Yu Yongjae , Zhao Xiang , Qin Huafeng
Published: July 2021

Thellier-type paleointensity experiments associated with partial thermal remanent magnetization checks have been widely used to determine paleointensity values from volcanic and archaeological media. However, previous studies have revealed that a substantial portion of paleointensity results with positive checks for historical lava samples largely fails to predict known Earth magnetic field intensity values. To determine the fidelity of paleointensity values, conventional Thellier-type paleointensity experiments were performed on Kilauea lava flows that erupted in 1960. The positive partial thermal remanent magnetization checks for our results range from 30.28 ± 1.38 µT to 52.94 ± 1.89 µT. This strongly indicates that conventional paleointensity checks cannot guarantee the fidelity of paleointensity results, especially when the unblocking temperatures for the newly formed magnetic particles are higher than the treatment temperature. Therefore, in this study, to check for thermal alteration during heating, the temperature dependence of the hysteresis parameter measured at room temperature for the thermally treated samples was also measured. Our new results show that nearly all biased paleointensity values correspond to a ratio of the coercivity of remanence to the magnetic coercivity of > 3 and a chemical alteration index > ~ 10%, which indicates the strong effect of the domain state and thermal alteration on the fidelity of the paleointensity results. Our study provides feasible criteria to further improve the fidelity of paleointensity estimations.
Relationship between the structure and function of the transcriptional regulator E2A
Authors: Liang Jia-Jie , Peng Hu , Wang Jiao-Jiao , Liu Xiao-Hui , Ma Lan , Ni Yi-Ran , Yang Huai-Jie , Zhang Yan-Qiong , Ai Wen-Bing , Wu Jiang-Feng
Published: July 2021

E proteins are transcriptional regulators that regulate many developmental processes in animals and lymphocytosis and leukemia in Homo sapiens. In particular, E2A, a member of the E protein family, plays a major role in the transcriptional regulatory network that promotes the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation usually requires the formation of E2A dimers, which then bind to coregulators. In this review, we summarize the mechanisms by which E2A participates in transcriptional regulation from a structural perspective. More specifically, the C-terminal helix-loop-helix (HLH) region of the basic HLH (bHLH) domain first dimerizes, and then the activation domains of E2A bind to different coactivators or corepressors in different cell contexts, resulting in histone acetylation or deacetylation, respectively. Then, the N-terminal basic region (b) of the bHLH domain binds to or dissociates from a specific DNA motif (E-box sequence). Last, trans-activation or trans-repression occurs. We also summarize the properties of these E2A domains and their interactions with the domains of other proteins. The feasibility of developing drugs based on these domains is discussed.
Complete closure of a colo-duodenal fistula in a patient with advanced ascending colon cancer after pembrolizumab combined with radiation therapy: a case report
Authors: Tominaga Tetsuro , Nonaka Takashi , Fukuda Akiko , Moriyama Masaaki , Oyama Shosaburo , Ishii Mitsutoshi , Nishimuta Masato , Fujise Yuta , Sawai Terumitsu , Nagayasu Takeshi
Published: July 2021

Background

A colo-duodenal fistula is a very rare complication of colon cancer that presents with not only severe clinical symptoms, but a poor prognosis due to locally advanced cancer. A novel immune checkpoint inhibitor for colon cancer patients provides a high objective response rate. Recently, radiation therapy combined with immune checkpoint inhibitor therapy has been reported to have a synergistic antitumor effect. A case of complete closure of a colo-duodenal fistula in a patient with locally advanced colon cancer after combined pembrolizumab and radiation therapy is reported.

Case presentation

A 66-year-old man presented with abdominal distention. Abdominal contrast-enhanced computed tomography (CT) showed a 80-mm bulky mass in the right upper quadrant. The tumor created a fistula to the second portion of the duodenum. Upper gastrointestinal endoscopy showed a colo-duodenal fistula. Gastro-jejunal bypass and ileostomy were performed to prevent bowel obstruction, followed by systemic chemotherapy. MSI-high was diagnosed on examination of the biopsy specimen. Treatment was then changed to immunotherapy using pembrolizumab; after six courses, the tumor markers were decreased to within normal ranges, but the main tumor increased. Radiation therapy was then given for local control of the main tumor, after which CT showed that all of the tumor, including the main tumor, lymph node metastases, and the colo-duodenal fistula, had gradually shrunk. Follow-up upper gastrointestinal endoscopy showed that the colo-duodenal fistula had closed completely. PET–CT showed no abnormal uptake in all tumors, and clinical complete response was diagnosed. Now, 21 months after diagnosis, the tumor is well controlled without evidence of regrowth.

Conclusions

Pembrolizumab combined with radiation therapy has a potentially dramatic therapeutic effect for advanced colon cancer.
Acute mental health presentations before and during the COVID-19 pandemic
Authors: Mukadam Naaheed , Sommerlad Andrew , Wright Jessica , Smith Abigail , Szczap Aleksandra , Solomou Solomis , Bhome Rohan , Thayalan Roshan , Abrol Esha , Aref-Adib Golnar , Maconick Lucy , Aubrey-Jones Dominic , Tugrul Senem , Knowles Melanie , Menys Helen , Sathanandan Shivanthi , Moslehi Sarah , Huntley Jonathan , Liu Kathy , Carlos Bazo-Alvarez Juan
Published: July 2021

Background

A number of community based surveys have identified an increase in psychological symptoms and distress but there has been no examination of symptoms at the more severe end of the mental health spectrum.

Aims

We aimed to analyse numbers and types of psychiatric presentations to inform planning for future demand on mental health services in light of the COVID-19 pandemic.

Method

We analysed electronic data between January and April 2020 for 2534 patients referred to acute psychiatric services, and tested for differences in patient demographics, symptom severity and use of the Mental Health Act 1983 (MHA), before and after lockdown. We used interrupted time-series analyses to compare trends in emergency department and psychiatric presentations until December 2020.

Results

There were 22% fewer psychiatric presentations the first week and 48% fewer emergency department presentations in the first month after lockdown initiated. A higher proportion of patients were detained under the MHA (22.2 v. 16.1%) and Mental Capacity Act 2005 (2.2 v. 1.1%) (χ2(2) = 16.3, P < 0.0001), and they experienced a longer duration of symptoms before seeking help from mental health services (χ2(3) = 18.6, P < 0.0001). A higher proportion of patients presented with psychotic symptoms (23.3 v. 17.0%) or delirium (7.0 v. 3.6%), and fewer had self-harm behaviour (43.8 v. 52.0%, χ2(7) = 28.7, P < 0.0001). A higher proportion were admitted to psychiatric in-patient units (22.2 v. 18.3%) (χ2(6) = 42.8, P < 0.0001) after lockdown.

Conclusions

UK lockdown resulted in fewer psychiatric presentations, but those who presented were more likely to have severe symptoms, be detained under the MHA and be admitted to hospital. Psychiatric services should ensure provision of care for these patients as well as planning for those affected by future COVID-19 waves.
Real-World Data on Adult T-Cell Leukemia/Lymphoma in Latin America: A Study From the Grupo de Estudio Latinoamericano de Linfoproliferativos
Authors: Malpica Luis , Enriquez Daniel J. , Castro Denisse A. , Peña Camila , Idrobo Henry , Fiad Lorena , Prates Maria , Otero Victoria , Biglione Mirna , Altamirano Milagros , Sandival-Ampuero Gustavo , Aviles-Perez Ursula , Meza Kelly , Aguirre-Martinez Laura , Cristaldo Nancy , Maradei Juan L. , Guanchiale Luciana , Soto Pablo , Viñuela Jose L. , Cabrera Maria E. , Paredes Sally Rose , Riva Eloisa , Di Stefano Marcos , Noboa Andrea , Choque Juan A. , Candelaria Myrna , Von Glasenapp Alana , Valvert Fabiola , Torres-Viera Maria A. , Castillo Jorge J. , Ramos Juan Carlos , Villela Luis , Beltran Brady E.
Published: July 2021

PURPOSE

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking.

PATIENTS AND METHODS

We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test.

RESULTS

We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone–like regimen ( P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%.

CONCLUSION

This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.
Rising Inequality in Mothers' Employment Statuses: The Role of Intergenerational Transmission
Authors: Binder Ariel J.
Published: July 2021

During the late twentieth century, U.S. mothers' propensities to hold full-time jobs became increasingly unequal across the distribution of socioeconomic status (SES). Consequently, daughters in high-SES households became more likely to be raised by working mothers than daughters in low-SES households. To what extent did this unequal exposure further shape maternal employment inequality in the twenty-first century—when these daughters had grown into adults and begun to raise their own children? Leveraging the genealogical structure of the Panel Study of Income Dynamics, this article estimates intergenerational employment coefficients on a sample of late twentieth century mothers and their daughters. It documents a much stronger intergenerational relationship in high-SES families than in low-SES families. Supplementary analyses reveal that being raised by a working mother significantly reduces the motherhood employment penalty among high-SES women but not among low-SES women. Unequal rates of mother-daughter employment transmission by SES can account for 36% of growing inequality in maternal employment across SES groups, observed in the Current Population Survey, between 1999 and 2016. These findings indicate that family-level transmission processes magnify the effects of structural forces on maternal employment inequality.
Cohort profile for the STratifying Resilience and Depression Longitudinally (STRADL) study: A depression-focused investigation of Generation Scotland, using detailed clinical, cognitive, and neuroimaging assessments
Authors: Habota Tina , Sandu Anca-Larisa , Waiter Gordon D. , McNeil Christopher J. , Steele J. Douglas , Macfarlane Jennifer A. , Whalley Heather C. , Valentine Ruth , Younie Dawn , Crouch Nichola , Hawkins Emma L. , Hirose Yoriko , Romaniuk Liana , Milburn Keith , Buchan Gordon , Coupar Tessa , Stirling Mairi , Jagpal Baljit , MacLennan Beverly , Priba Lucasz , Harris Mathew A. , Hafferty Jonathan D. , Adams Mark J. , Campbell Archie I. , MacIntyre Donald J. , Pattie Alison , Murphy Lee , Reynolds Rebecca M. , Elliot Rebecca , Penton-Voak Ian S. , Munafò Marcus R. , Evans Kathryn L. , Seckl Jonathan R. , Wardlaw Joanna M. , Lawrie Stephen M. , Haley Christopher S. , Porteous David J. , Deary Ian J. , Murray Alison D. , McIntosh Andrew M.
Published: July 2021

STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS provides an important opportunity to study complex gene-environment interactions, incorporating linkage to existing datasets and inclusion of early-life variables for two longitudinal birth cohorts. Specifically, data collection in STRADL included: socio-economic and lifestyle variables; physical measures; questionnaire data that assesses resilience, early-life adversity, personality, psychological health, and lifetime history of mood disorder; laboratory samples; cognitive tests; and brain magnetic resonance imaging. Some of the questionnaire and cognitive data were first assessed at the GS:SFHS baseline assessment between 2006-2011, thus providing longitudinal measures relevant to the study of depression, psychological resilience, and cognition. In addition, routinely collected historic NHS data and early-life variables are linked to STRADL data, further providing opportunities for longitudinal analysis. Recruitment has been completed and we consented and tested 1,188 participants.
Film Tourism for Heritage Conservation and Promotion
Authors: Mohanty Priyakrushna , Thomas Anila , Pudota Harshitha , Deka Meghna
Published: July 2021

Film tourism has been recognized as a key instrument in the process of destination development and co-creation of tourist experiences. The promotion of any destination through films can result in attracting more visitors and subsequently, formulation of policies favoring that destination which aid in the conservation and promotion of the tangible and intangible cultural heritage of the place. In this context, this article analyses the case of Nrityagram, a village formed by the international community of Indian classical dancers. The work highlights the possibility that if promoted as a film tourism destination, Nrityagram can contribute to the promotion and conservation of Indian cultural dance, a form of intangible heritage. The work is primarily qualitative in nature and draws upon existing literature as well as the experiences gained from the field visit made to the said site.
Visitor Management at UNWHS
Authors: Suklabaidya Paramita , Aggarwal Monika
Published: July 2021

Studies have shown a significant increase in the number of visitors to the site after being featured on the UNWHS list which leads to visitation pressure and impacts thereof on the site. Visitor management at the UNWHS is the need of the hour. The paper aims to critically analyse the existing visitor management plan at the selected UNWHS - Taj Mahal, the second-best UNWHS in the world with more than 8 million visitors every year (timesofindia.indiatimes.com, tribuneindia.com, indiatoday. in, hindustantimes.com, 2017), and to suggest numerous proactive and reactive measures to bring about an effective Visitor Management strategy for the Site. The descriptive and exploratory research methodology has been used along with a mixed approach of both Quantitative and Qualitative Methods. Literature review of Visitor Management practices followed at UNWHS globally and an in-depth study of opinion of different groups – Site Managers, Travel agents, Guides, Visitors visiting the site helped conclude, that to defy the harmful impact of the visitation and to give an enhanced experience, an effective marketing plan with strict conservation and preservation practices have to be implemented in collaboration with locals, stakeholders and the government agencies
Global Food Trade in a Rule Based System
Authors: Alex Ann Thania
Published: July 2021

A rule-based regime of international trade is built upon norms of equality and non-discrimination. It helps maintain equity in international trade by the observance of principles such as that of Most Favoured Nation and National Treatment. A closer inspection of the sector wise international trade practices of nations suggests that there are deviations from the rule-based mechanism of World Trade Organisation. This detrimentally impacts the balance of trade. This research article analyses the application of the rule-based regime of the World Trade Organisation with special reference to instances of inequalities in regulations imposed on trade in food products in the context of India and other developing countries. The paper concludes with an analysis of the plausible reasons for the rejection of exports from developing countries and suggests the need for the rectification of such inequalities.
Drunkorexia – knowledge review
Authors: Szynal Kamila , Górski Michał , Grajek Mateusz , Ciechowska Karolina , Polaniak Renata
Published: July 2021

Zaburzeniom odżywiania często towarzyszy brak umiejętności radzenia sobie z emocjami. Alkoreksja jest zjawiskiem, które występuje głównie wśród grupy studentów. Zaburzenie to charakteryzuje się występowaniem znacznych restrykcji żywieniowych oraz nadmiernej aktywności fizycznej celem możliwości spożycia większej ilości alkoholu bez obawy o przyrost masy ciała. Jej podstawy upatruje się w presji rówieśników, popularyzowaniu szczupłej sylwetki oraz chęci zwiększenia stanu odurzenia. Kobiety częściej zgłaszają występowanie drunkoreksji wraz z występowaniem innych zaburzeń odżywiania. Jak każde zaburzenia odżywiania, alkoreksja może prowadzić do poważnych konsekwencji zdrowotnych, lecz także zwiększenia ryzyka przemocy, napaści na tle seksualnym i wypadków samochodowych. Drunkoreksja wymaga leczenia uzależnienia alkoholu oraz korekty nieodpowiednich nawyków żywieniowych. Alkoreksja jest terminem stosunkowo nowym i wymaga opracowania kryteriów rozpoznania oraz strategii pomocy osobom zmagającym się z tym zaburzeniem. Należy odróżnić alkoreksję od choroby alkoholowej i innych zaburzeń odżywiania. Konieczne jest szerzenie wiedzy na temat tego typu zachowań, ich konsekwencji oraz edukacja w zakresie radzenia sobie ze stresem.
Sexual disorders in the men treated in a psychiatric ward
Authors: Błachut Michał , Badura-Brzoza Karina , Ścisło Piotr , Bugdol Monika , Świerzy Krzysztof , Piegza Magdalena , Gorczyca Piotr
Published: July 2021

Cel pracy

Próba oceny wpływu podwójnej diagnozy na występowanie zaburzeń seksualnych oraz ocena problemów z funkcjonowaniem seksualnym mężczyzn leczonych w oddziale psychiatrycznym.

Metoda

W badaniu udział wzięło 140 mężczyzn hospitalizowanych psychiatrycznie (średnia wieku 40,4 ±12,7 lat) z rozpoznaniem schizofrenii, zaburzeń afektywnych, lękowych, uzależnień oraz podwójnej diagnozy (schizofrenii i uzależnienia). W badaniach użyto Kwestionariusza Seksuologicznego Kokoszki oraz Międzynarodowego Indeksu Funkcji Seksualnych IIEF-5.

Wyniki

Występowanie zaburzeń seksualnych w badanej grupie notowano u 83.6% pacjentów. Najczęściej obserwowano obniżenie potrzeb seksualnych (53.6%) i opóźnienie orgazmu (40%). Zaburzenia erekcji w zależności od zastosowanego narzędzia badawczego pojawiły się u 38.6% badanych (wg Kwestionariusza Kokoszki) i 61.4% badanych (IIEF-5). Ciężkie zaburzenia erekcji występowały częściej w grupie chorych nie posiadających partnera (12.4% vs 0; p=0.000) w porównaniu do osób w związkach oraz w grupie z zaburzeniami lękowymi (p=0.028) w porównaniu do grup z innymi zaburzeniami psychicznymi. W grupie osób z podwójną diagnozą (PD) zaburzenia seksualne obserwowano częściej w porównaniu do chorych na schizofrenię (p=0.034). Leczenie powyżej 5 lat wiązało się częściej z występowaniem zaburzeń seksualnych (p=0,007). W grupie PD brak orgazmu i nadmierne potrzeby seksualne występowały częściej w porównaniu do osób z jednym rozpoznaniem (p=0.0145; p=0.035).

Wnioski

Zaburzenia seksualne występują częściej w grupie chorych z PD w porównaniu do pacjentów z rozpoznaniem schizofrenii. Brak posiadania partnera oraz czas leczenia psychiatrycznego powyżej 5 lat wiąże się z częstszym występowaniem zaburzeń seksualnych.
"These forecasts may be substantially different from actual results." The use of epistemic modal markers in English and German original letters to shareholders and in English-German transla
Authors: Kranich Svenja , Bicsár Andrea
Published: July 2021

Letters to shareholders (i. e. the first part of a company's Annual Report) represent an interesting genre for the analysis of epistemic modal expressions. They serve the function to present a short overview of the company's main achievements as well as an outlook into the future. They additionally serve a more marketing-oriented goal: to inspire confidence in the company. Epistemic modal expressions (e. g. may, perhaps, probably) are used in texts for two main reasons: Firstly, speakers can signal with these markers that they have content-based reasons to be unsure about the states of affairs they are talking about. This type of use can be expected to be typical in the context of predictions of future developments. Secondly, speakers can use them for interpersonal reasons, to open up the discursive space for alternative positions, leaving the readers their right to form their own opinion. This type of use can be expected in positive evaluations of one's own company, which are thus presented in a mitigated way, avoiding the impression of boasting.It is in particular the second type of use that can be expected to be highly sensitive to cultural differences. The present paper analyzes to what extent US-English and German letters to shareholders differ in the use of these markers, and how these differences are reflected in English-German translations. Our quantitative analysis of the distribution of all epistemic modal markers in a multilingual corpus comes to the conclusion that there are notable differences between English and German original texts. Unlike in other studies on English-German translations (e. g. Kranich/House/Becher 2012), however, we arrive at the conclusion that the English-German translations are very closely adapted to the target-language conventions and show little interference from the English originals.
Generic Structure Potential of Christian Apologetics
Authors: Inya Onwu
Published: July 2021

Religious texts have been examined by scholars from different theoretical standpoints. However, a close survey of the literature reveals that little attention has been paid to Christian apologetics from a linguistic perspective. Also, an examination of studies along the lines of Generic Structure Potential (henceforth GSP) shows that the genre status of Christian apologetics has not been indicated. This gap provides the motivation for this paper, which investigates the GSP of Christian apologetics. Twenty texts written by various key contemporary apologetic writers were purposively selected for the study. The following generic structure potential catalogue was generated:

The paper reveals that the elements of the GSP concertedly work to advance, argue for or defend the Christian belief system. The paper also suggests that the model could be applied to other forms of apologetic instances.
Quantification of scar collagen texture and prediction of scar development via second harmonic generation images and a generative adversarial network
Authors: Wang Qing , Liu Weiping , Chen Xinghong , Wang Xiumei , Chen Guannan , Zhu Xiaoqin
Published: July 2021

Widely used for medical analysis, the texture of the human scar tissue is characterized by irregular and extensive types. The quantitative detection and analysis of the scar texture as enabled by image analysis technology is of great significance to clinical practice. However, the existing methods remain disadvantaged by various shortcomings, such as the inability to fully extract the features of texture. Hence, the integration of second harmonic generation (SHG) imaging and deep learning algorithm is proposed in this study. Through combination with Tamura texture features, a regression model of the scar texture can be constructed to develop a novel method of computer-aided diagnosis, which can assist clinical diagnosis. Based on wavelet packet transform (WPT) and generative adversarial network (GAN), the model is trained with scar texture images of different ages. Generalized Boosted Regression Trees (GBRT) is also adopted to perform regression analysis. Then, the extracted features are further used to predict the age of scar. The experimental results obtained by our proposed model are better compared to the previously published methods. It thus contributes to the better understanding of the mechanism behind scar development and possibly the further development of SHG for skin analysis and clinic practice.
Vision-correcting holographic display: evaluation of aberration correcting hologram
Authors: Kim Dongyeon , Nam Seung-Woo , Bang Kiseung , Lee Byounghyo , Lee Seungjae , Jeong Youngmo , Seo Jong-Mo , Lee Byoungho
Published: July 2021

Vision-correcting displays are key to achieving physical and physiological comforts to the users with refractive errors. Among such displays are holographic displays, which can provide a high-resolution vision-adaptive solution with complex wavefront modulation. However, none of the existing hologram rendering techniques have considered the optical properties of the human eye nor evaluated the significance of vision correction. Here, we introduce vision-correcting holographic display and hologram acquisition that integrates user-dependent prescriptions and a physical model of the optics, enabling the correction of on-axis and off-axis aberrations. Experimental and empirical evaluations of the vision-correcting holographic displays show the competence of holographic corrections over the conventional vision correction solutions.
Obesity and revision surgery, mortality, and patient-reported outcomes after primary knee replacement surgery in the National Joint Registry: A UK cohort study
Authors: Evans Jonathan Thomas , Mouchti Sofia , Blom Ashley William , Wilkinson Jeremy Mark , Whitehouse Michael Richard , Beswick Andrew , Judge Andrew
Published: July 2021

Background

One in 10 people in the United Kingdom will need a total knee replacement (TKR) during their lifetime. Access to this life-changing operation has recently been restricted based on body mass index (BMI) due to belief that high BMI may lead to poorer outcomes. We investigated the associations between BMI and revision surgery, mortality, and pain/function using what we believe to be the world’s largest joint replacement registry.

Methods and findings

We analysed 493,710 TKRs in the National Joint Registry (NJR) for England, Wales, Northern Ireland, and the Isle of Man from 2005 to 2016 to investigate 90-day mortality and 10-year cumulative revision. Hospital Episodes Statistics (HES) and Patient Reported Outcome Measures (PROMs) databases were linked to the NJR to investigate change in Oxford Knee Score (OKS) 6 months postoperatively.

After adjustment for age, sex, American Society of Anaesthesiologists (ASA) grade, indication for operation, year of primary TKR, and fixation type, patients with high BMI were more likely to undergo revision surgery within 10 years compared to those with “normal” BMI (obese class II hazard ratio (HR) 1.21, 95% CI: 1.10, 1.32 (p < 0.001) and obese class III HR 1.13, 95% CI: 1.02, 1.26 (p = 0.026)). All BMI classes had revision estimates within the recognised 10-year benchmark of 5%. Overweight and obese class I patients had lower mortality than patients with “normal” BMI (HR 0.76, 95% CI: 0.65, 0.90 (p = 0.001) and HR 0.69, 95% CI: 0.58, 0.82 (p < 0.001)). All BMI categories saw absolute increases in OKS after 6 months (range 18–20 points). The relative improvement in OKS was lower in overweight and obese patients than those with “normal” BMI, but the difference was below the minimal detectable change (MDC; 4 points). The main limitations were missing BMI particularly in the early years of data collection and a potential selection bias effect of surgeons selecting the fitter patients with raised BMI for surgery.

Conclusions

Given revision estimates in all BMI groups below the recognised threshold, no evidence of increased mortality, and difference in change in OKS below the MDC, this large national registry shows no evidence of poorer outcomes in patients with high BMI. This study does not support rationing of TKR based on increased BMI.
Prehabilitation to prevent complications after cardiac surgery - A retrospective study with propensity score analysis
Authors: Hartog Johanneke , Mousavi Iman , Dijkstra Sandra , Fleer Joke , van der Woude Lucas H. V. , van der Harst Pim , Mariani Massimo A.
Published: July 2021

Background

The rising prevalence of modifiable lifestyle-related risk factors (e.g. overweight and physical inactivity) suggests the need for effective and safe preoperative interventions to improve outcomes after cardiac surgery. This retrospective study explored potential short-term postoperative benefits and unintended consequences of a multidisciplinary prehabilitation program regarding in-hospital complications.

Methods

Data on patients who underwent elective cardiac surgery between January 2014 and April 2017 were analyzed retrospectively. Pearson’s chi-squared tests were used to compare patients who followed prehabilitation (three times per week, at a minimum of three weeks) during the waiting period with patients who received no prehabilitation. Sensitivity analyses were performed using propensity-score matching, in which the propensity score was based on the baseline variables that affected the outcomes.

Results

Of 1201 patients referred for elective cardiac surgery, 880 patients met the inclusion criteria, of whom 91 followed prehabilitation (53.8% ≥ 65 years, 78.0% male, median Euroscore II 1.3, IQR, 0.9–2.7) and 789 received no prehabilitation (60.7% ≥ 65 years, 69.6% male, median Euroscore II 1.6, IQR, 1.0–2.8). The incidence of atrial fibrillation (AF) was significantly lower in the prehabilitation group compared to the unmatched and matched standard care group (resp. 14.3% vs. 23.8%, P = 0.040 and 14.3% vs. 25.3%, P = 0.030). For the other complications, no between-group differences were found.

Conclusions

Prehabilitation might be beneficial to prevent postoperative AF. Patients participated safely in prehabilitation and were not at higher risk for postoperative complications. However, well-powered randomized controlled trials are needed to confirm and deepen these results.