bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Outcomes by Surgical Approach in Patients with Malignant Sinonasal Disease
Authors: Lenze Nicholas R. , Quinsey Carolyn , Sasaki-Adams Deanna , Ewend Matthew G. , Thorp Brian D. , Ebert Charles S. , Zanation Adam M.
Published: May 2021

Objective There is a paucity of data on comparative outcomes for open versus endoscopic surgery for patients with malignant sinonasal pathology. Most of the available studies are limited by a sample size <100 patients.

Design This is a retrospective cohort study.

Setting The findings of this study come from a single-institution tertiary care center from 2008 to 2019.

Participants In total, 199 patients who underwent surgery for malignant sinonasal disease participated in this study.

Main Outcome Measures The main outcome measures were perioperative complications and reoperation.

Results Patients in our sample had a mean age of 59.7 years (SD, 20.4). In total, 62% were male and 72% were white. An endoscopic-only approach was used in 41% of patients and an open or combined approach in 59% of patients. Squamous cell carcinoma was the most common pathology (43.0%), followed by sarcoma (9.5%), skin cancer (6.5%), sinonasal undifferentiated carcinoma (6.5%), and adenocarcinoma (5.5%). The all-cause complication rate was 14.6%. Patients with an open resection had a higher rate of intraoperative complications (5.9 vs. 0%; p = 0.043), postoperative complications (19.5 vs. 3.7%; p = 0.001), and all-cause complications (21.0 vs. 3.7%; p < 0.001). The likelihood of early reoperation (<6 months) or late reoperation (>6 months) did not significantly differ by surgical approach (p = 1.000 and 0.741, respectively).

Conclusion The endoscopic approach for resection of malignant sinonasal disease is viable for select patients and may be associated with a favorable complication rate compared with the open approach.
Leiomyosarcoma of Uterus in a Nulliparous Female: Mimicking as Ovarian Malignancy
Authors: Mishra Jagannath , Bhattacharya Supratim , Pandia Arpita , Padhy Ashok , Mahapatra Manoranjan , Mohapatra Janmejay
Published: May 2021

Uterine sarcoma is a rare verity of smooth muscle tumor, accounting for 2 to 6% of uterine malignancies. Leiomyosarcoma (LMS) represents ∼1% of overall uterine tumors and ∼25 to 36% of uterine sarcomas. Here we present a case of uterine LMS in a 34-year-old nulliparous woman presented with huge distension of abdomen which was confused to be an ovarian malignancy. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The diagnosis of LMS is made by histopathological examination after surgery. Surgery is the only treatment and role of adjuvant therapy has not been clearly defined.
Two Rare Syndromic Syndactyly Cases in Neonates
Authors: Kamath Pooja Prabhakar
Published: May 2021

Introduction Isolated findings of syndactyly are benign. However, syndactyly can be associated with rare syndromes that need to be diagnosed for further management and for genetic counseling.

Methods We present two cases of syndromic syndactyly in neonates. The first case is a 13-day-old female neonate with dysmorphic features. The neonate had clinical features of prominent forehead, hypertelorism, widely separated sagittal and metopic sutures, down-slanting eyes, low set ears, depressed nasal bridge, micrognathia, cleft palate, pectus excavatum, brachydactyly, and syndactyly of the second to fourth fingers bilaterally in upper limbs and in lower limbs.

The second case is a 10-day-old male neonate with dysmorphism in the form of cleft alveolar ridge and palate, hyperplastic frenula, hypoplastic alar cartilage, syndactyly of the left hand, clinodactyly of the left lower limb toes, and amniotic bands.

Discussion Case 1 was diagnosed as otopalatodigital syndrome because of the characteristic clinical features. This is a rare syndrome associated with syndactyly that often goes undiagnosed. Otopalatodigital syndrome spectrum disorders comprise of four phenotypically related conditions: otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia, and Melnick–Needles syndrome. As it is associated with x-linked inheritance, its severity is more in males.

Case 2 was diagnosed to have orofaciodigital syndrome because of the characteristic clinical features. It is another rare syndrome associated with syndactyly having abnormalities in the development of the oral cavity, face, and digits along with intellectual disability and renal system impairment.

Conclusion There are fewer publications on these syndromes as they are rare and diagnosis is difficult. Recognizing these syndromes is key to further management and for genetic counseling.
A Prospective Evaluation of Quality of Life in Patients Undergoing Extended Endoscopic Endonasal Surgery for Benign Pituitary Gland Lesion
Authors: Carmel Neiderman Narin Nard , Wengier Anat , Dominsky Omri , Ringel Barak , Warshavsky Anton , Horowitz Gilad , Baran Tomer Ziv , Ram Zvi , Grossman Rachel , Fliss Dan Marian , Avraham Abergel
Published: May 2021

Introduction Endoscopic endonasal surgery (EES) has become the preferred approach for pituitary tumor resection. Nevertheless, research on quality of life related to pituitary adenoma surgery is scarce.

Objective The aim of the study is to evaluate short-term quality of life in patients after endoscopic endonasal resection of pituitary tumors and to find predictors for poor quality of life (QOL) outcome.

Materials and Methods A prospective cohort study was conducted, including all patients who underwent EES for pituitary tumors in a tertiary medical referral center. Recruited patients completed the Anterior Skull Base Disease-Specific QOL (ASBS-Q) questionnaire and the Sinonasal Outcome Test 22 (SNOT-22) questionnaire before surgery, 2 and 4 to 6 months after surgery. Demographic and clinical data was collected.

Results Our study included 49 patients. The overall ASBS-Q scores significantly improved 4 to 6 months after surgery (4.46 vs. 4.2, p < 0.05). We found a significant improvement in QOL related to emotional state 2 months post surgery (4.41 vs. 3.87, p < 0.05), which became borderline significant 4 to 6 months post surgery. There was a significant improvement in pain (4.5 vs. 4.08, p < 0.05) and vitality (4.43 vs. 4.16, p < 0.05) domains 4 to 6 months post surgery. SNOT-22 scores did not change significantly postoperatively. Factors such as secreting and non-secreting tumors, tumor size, intraoperative cerebrospinal fluid leak, gross tumor resection, endocrine remission, and the use of nasoseptal flap reconstruction did not have a significant effect on QOL.

Conclusion We found that patients after EES reported improved QOL 4 to 6 months post surgery. Specific improvement was noted in the QOL related to pain and vitality.
DGIV Nachrichten: Anregungen zur Zukunft der integrierten Versorgung nach der Wahl
Authors: Kloepfer Albrecht
Published: May 2021

Die Bundestagswahl steht vor der Tür – ein Aufruf an die Deutsche Gesellschaft für Integrierte Versorgung (DGIV), in einem Positionspapier ihre Überlegungen zu konkretisieren. An dieser Stelle eine Zusammenfassung unserer Forderungen an die Politik.
Factor investing and asset allocation strategies: a comparison of factor versus sector optimization
Authors: Bessler Wolfgang , Taushanov Georgi , Wolff Dominik
Published: May 2021

Given the tremendous growth of factor allocation strategies in active and passive fund management, we investigate whether factor or sector asset allocation strategies provide investors with a superior performance. Our focus is on comparing factor versus sector allocations as some recent empirical evidence indicates the dominance of sector over country portfolios. We analyze the performance and performance differences of sector and factor portfolios for various weighting and portfolio optimization approaches, including “equal-weighting” (1/N), “risk parity,” minimum-variance, mean-variance, Bayes–Stein and Black–Litterman. We employ a sample-based approach in which the sample moments are the input parameters for the allocation model. For the period from May 2007 to November 2020, our results clearly reveal that, over longer investment horizons, factor portfolios provide relative superior performances. For shorter periods, however, we observe time-varying and alternating performance dominances as the relative advantage of one over the other strategy depends on the economic cycle. One important insight is that during “normal” times factor portfolios clearly dominate sector portfolios, whereas during crisis periods sector portfolios are superior offering better diversification opportunities.
Sporisorium sacchari (Asian sugarcane smut).
Authors:   USA, USDA-ARS
Published: May 2021

Little published information exists on this plant pathogenic fungus of limited geographic distribution. S. sacchari is one of several Asian species only parasitizing the flowers of Saccharum species, thus causing much less damage to the plants than does the more widespread sugarcane smut that infects buds and reduces the growth of shoots. Although windborne, and probably contaminating seeds, S. sacchari spreads less well with the vegetatively propagated cane plants. Nevertheless, its effects on other possible hosts could pose a threat to native or agricultural plants if it were introduced.
Conotrachelus nenuphar (plum curculio).
Authors: Vincent Charles
Published: May 2021

The plum curculio, C. nenuphar, is native to North America and restricted to east of the Rocky Mountains. Although it feeds on several wild host plants and several species of cultivated pome and stone fruit, C. nenuphar has not extended its geographical range over the years. Given its life-cycle (larvae complete their development and diapause in the soil), it is not likely to be a global invasive species. It can be considered as a local invader, as it will invade any new orchard plant (apple: Malus; plum: Prunus; peach: Prunus) and thereby become a serious pest of these agricultural habitats.
Globodera pallida (white potato cyst nematode).
Authors: Rowe Janet
Published: May 2021

G. pallida originates from the Andes and is known to be present in 55 countries. It is found predominantly in temperate regions as is the related species, Globodera rostochiensis. It is possibly more difficult to manage than G. rostochiensis because there is currently less resistance available in commercially-grown potato cultivars. Egg-laden cysts are the most environmentally resistant and easily transportable stage in the parasites life cycle, and are found in soil particles, on host roots, stolons or tubers. The microscopic size of the cyst makes it difficult to detect, and it can successfully establish new infestations when an appropriate climate and host plant are available. Machinery used on infested land followed by use in otherwise uninfested areas is a common method of spread, for example, fumigation equipment that has not been cleaned before use in another area. Disinfection of farming tools, transport and clothing helps to keep uninfested land free from G. pallida. Wind, rain and flood water are also capable of redistributing viable cysts to create new infestations.
Observation of large in-plane anisotropic transport in van derWaals semiconductor Nb2SiTe4
*
Authors: Zhou Kaiyao , Deng Jun , Chen Long , Xia Wei , Guo Yanfeng , Yang Yang , Guo Jian-Gang , Guo Liwei
Published: May 2021

Two-dimensional (2D) van der Waals material is a focus of research for its widespread application in optoelectronics, memories, and spintronics. The ternary compound Nb2SiTe4 is a van der Waals semiconductor with excellent air stability and small cleavage energy, which is suitable for preparing a few layers counterpart to explore novel properties. Here, properties of bulk Nb2SiTe4 with large in-plane electrical anisotropy are demonstrated. It is found that hole carriers dominate at a temperature above 45 K with a carrier active energy of 31.3 meV. The carrier mobility measured at 100 K is about 213 cm2⋅V−1⋅s−1 in bulk Nb2SiTe4, higher than the reported results. In a thin flake Nb2SiTe4, the resistivity ratio between the crystalline axes of a and b is reaching about 47.3 at 2.5 K, indicating that there exists a large anisotropic transport behavior in their basal plane. These novel transport properties provide accurate information for modulating or utilizing Nb2SiTe4 for electronic device applications.
Tunable inhibition of β-amyloid peptides by fast green molecules*
Authors: Yang Tiantian , Yu Tianxiang , Zhao Wenhui , Lin Dongdong
Published: May 2021

The aggregation of β-amyloid (Aβ) protein into toxic intermediates and mature fibrils is considered to be one of the main causes of Alzheimer’s disease (AD). Small molecules as one of blockers are expected to be the potential drug treatment for the disease. However, the nucleation process in molecular assembly is less informative in the literatures. In this work, the formation of Aβ(16-22) peptides was investigated with the presence of small molecule of fast green (FG) at the initial aggregation stage. The results exhibited the tunable inhibitory ability of FG molecules on Aβ(16-22) peptides. Atomic force microscopy (AFM) demonstrated that the inhibitory effect would be dependent on the dose of FG molecules, which could delay the lag time (nucleation) and form single layer conjugates. Spectral measurements further showed that the β-sheet secondary structure of Aβ(16-22) reduced dramatically after the presence of FG molecules. Instead, non-β-sheet nanosheets were formed when the FG/Aβ(16-22) ratio reached 1:1. In addition, the cytotoxicity of aggregates reduced greatly with the presence of FG molecules compared with the Aβ(16-22) fibrils. Overall, this study provided a method for suppressing the toxic amyloid aggregates by FG molecules efficiently, and also showed a strategy for fabrication of two-dimensional materials by small molecules.
Controllable preparation and disorder-dependent photoluminescence of morphologically different C60 microcrystals*
Authors: Cui Wen , Li De-Jun , Guo Jin-Liang , Zhao Lang-Huan , Liu Bing-Bing , Sun Shi-Shuai
Published: May 2021

Different C60 crystals were synthesized by precipitation from a mixture of the good solvent m-xylene and the poor solvent isopropyl alcohol. The samples were characterized by scanning electron microscopy (SEM), Raman spectroscopy, thermogravimetric analysis, and high resolution transmission electron microscope (HRTEM). We found that the morphologies and sizes of the samples could be controlled by adjusting the volume ratio between the good and poor solvents. Especially, an unexpected short flower column-like crystal was synthesized at low ratios (from 1:6 to 1:12). Room temperature photoluminescence (PL) and HRTEM studies of the C60 crystal samples reveal that the PL efficiency of the crystals decreases with increasing crystalline order and that the disordered C60 crystals synthesized at the ratio of 1:2 show 10 times higher PL efficiency than that of pristine C60. The mechanism of the growth process of these C60 crystals was also studied by replacing the good solvents m-xylene with toluene and mesitylene.
Fractal microstructure of Ag film via plasma discharge as SERS substrates*
Authors: Kan Xue-Fen , Yin Cheng , Cao Zhuang-Qi , Su Wei , Shan Ming-Lei , Wang Xian-Ping
Published: May 2021

According to the atmospheric pressure plasma (APP) technology, we propose a rapid synthetic approach of the substrates for enhanced Raman spectroscopy. The plasma is used to modify and etch the surface of silver film, which generates large scale hotspots’ aggregation. By switching the discharge polarity and adjusting the film thickness, different surface morphologies are formed due to the oxidation, reactive etch and accumulation of the plasma product in a certain space. Especially under positive corona discharge condition, dense snake-like microstructures are formed by the gradual connection of individual nanoparticles, which are driven by the influence of the electric field on surface diffusion. In addition, the experiments verify that the corresponding enhancement factor (EF) raises at least five orders of magnitude and the treatment time is about 10 min.
Excess-iron driven spin glass phase in Fe1 + y
Te1 – x
Se
x

*
Authors: Tian Long , Liu Panpan , Hong Tao , Seydel Tilo , Lu Xingye , Luo Huiqian , Li Shiliang , Dai Pengcheng
Published: May 2021

The iron-chalcogenide superconductor FeTe1–x
Se
x
displays a variety of exotic features distinct from iron pnictides. Although much effort has been devoted to understanding the interplay between magnetism and superconductivity near x = 0.5, the existence of a spin glass phase with short-range magnetic order in the doping range (x ∼ 0.1–0.3) has rarely been studied. Here, we use DC/AC magnetization and (quasi) elastic neutron scattering to confirm the spin-glass nature of the short-range magnetic order in a Fe1.07Te0.8Se0.2 sample. The AC-frequency dependent spin-freezing temperature T
f generates a frequency sensitivity ΔT
f(ω)/[T
f(ω)Δlog10
ω] ≈ 0.028 and the description of the critical slowing down with τ = τ
0(T
f/T
SG – 1)−z v
gives T
SG ≈ 22 K and zv ≈ 10, comparable to that of a classical spin-glass system. We have also extended the frequency-dependent T
f to the smaller time scale using energy-resolution-dependent neutron diffraction measurements, in which the T
N of the short-range magnetic order increases systematically with increasing energy resolution. By removing the excess iron through annealing in oxygen, the spin-freezing behavior disappears, and bulk superconductivity is realized. Thus, the excess Fe is the driving force for the formation of the spin-glass phase detrimental to bulk superconductivity.
Angular dependence of vertical force and torque when magnetic dipole moves vertically above flat high-temperature superconductor*
Authors: Yang Yong , Yang Shuai-Jie , Yang Wen-Li , Wu Yun-Yi
Published: May 2021

The interaction between a permanent magnet (PM) assumed as a magnetic dipole and a flat high-temperature superconductor (HTS) is calculated by the advanced frozen-image model. When the dipole vertically moves above the semi-infinite HTS, the general analytical expression of vertical force and that of torque are obtained for an arbitrary angle between the magnetization direction of the PM and the c axis of the HTS. The variations of the force and torque are analyzed for angle and vertical movements in both zero-field cooling (ZFC) condition and field cooling (FC) condition. It is found that the maximum vertical repulsive or attractive force has the positive or negative cosine relation with the angle. However, the maximum torque has the positive or negative sine relation. From the viewpoint of the rotational equilibrium, the orientation of the magnetic dipole with zero angle is deemed to be an unstable equilibrium point in ZFC, but the same orientation is considered as a stable equilibrium point in FC. In addition, both of the variation cycles of the maximum force and torque with the angle are π.
Comparative genome analysis using sample-specific string detection in accurate long reads
Authors: Khorsand Parsoa , Denti Luca ,   Human Genome Structural Variant Consortium, Bonizzoni Paola , Chikhi Rayan , Hormozdiari Fereydoun
Published: May 2021

Motivation

Comparative genome analysis of two or more whole-genome sequenced (WGS) samples is at the core of most applications in genomics. These include the discovery of genomic differences segregating in populations, case-control analysis in common diseases and diagnosing rare disorders. With the current progress of accurate long-read sequencing technologies (e.g. circular consensus sequencing from PacBio sequencers), we can dive into studying repeat regions of the genome (e.g. segmental duplications) and hard-to-detect variants (e.g. complex structural variants).

Results

We propose a novel framework for comparative genome analysis through the discovery of strings that are specific to one genome (‘samples-specific’ strings). We have developed a novel, accurate and efficient computational method for the discovery of sample-specific strings between two groups of WGS samples. The proposed approach will give us the ability to perform comparative genome analysis without the need to map the reads and is not hindered by shortcomings of the reference genome and mapping algorithms. We show that the proposed approach is capable of accurately finding sample-specific strings representing nearly all variation (>98%) reported across pairs or trios of WGS samples using accurate long reads (e.g. PacBio HiFi data).

Availability and implementation

Data, code and instructions for reproducing the results presented in this manuscript are publicly available at https://github.com/Parsoa/PingPong.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
Multi-omics reveals a relationship between endometrial amino acid metabolism and autophagy in women with recurrent miscarriage
Authors: Hong Ling , Zhu Yuan Chang , Liu Su , Wu Tonghua , Li Yuye , Ye Lijun , Diao Lianghui , Zeng Yong
Published: May 2021

Deterioration of the endometrial environment is an essential cause of recurrent miscarriage (RM). However, current studies in terms of endometrial amino acid metabolic characterization and autophagy are still inadequate. We tried to (1) identify the alternation in metabolite profiles in the RM endometrium; (2) investigate the expression of autophagy-related proteins in RM; and (3) elucidate the association between amino acid metabolism and autophagy in RM. Our results showed that glutamine metabolites were up-regulated in the endometrium of RM women. The levels of autophagy-associated proteins, LC3B, ATG12, and Beclin-1, were significantly higher in RM. Hemostasis, autophagy and IFNα signaling were the top three differentially activated signaling pathways between women with RM and normal pregnancy. Interestingly the expression of AMPK and GCN2 was significantly up-regulated in the endometrium of women with RM, and the same expression trend was also observed in the human endometrial stromal cells cultured in glutamine deprivation medium. Furthermore, inhibition of AMPK decreased the level of GCN2, indicating a positive correlation between GCN2 and AMPK. The expression of GCN2 was consistent with the expression of ATG12 and beclin-1; however, it was opposite to that of p62. Exposure to glutamine deprivation increased the level of LC3B, GCN2, ATG12, and beclin-1. Altogether, these findings suggested significant crosstalk between amino acid metabolism and autophagy. In summary, our data suggested that aberrant crosstalk between amino acid metabolism and autophagy may contribute to the impaired endometrial microenvironment of RM. Our study may provide new insight into the diagnosis of RM due to endometrial factors.
Liver resection and ablation for squamous cell carcinoma liver metastases
Authors: Engstrand J , Abreu de Carvalho L F , Aghayan D , Balakrishnan A , Belli A , Björnsson B , Dasari B V M , Detry O , Di Martino M , Edwin B , Erdmann J , Fristedt R , Fusai G , Gimenez-Maurel T , Hemmingsson O , Hidalgo Salinas C , Isaksson B , Ivanecz A , Izzo F , Knoefel W T , Kron P , Lehwald-Tywuschik N , Lesurtel M , Lodge J P A , Machairas N , Marino M V , Martin V , Paterson A , Rystedt J , Sandström P , Serrablo A , Siriwardena A K , Taflin H , van Gulik T M , Yaqub S , Özden İ , Ramia J M , Sturesson C ,   on behalf of the E-AHPBA Scientific and Research Committee
Published: May 2021

Background

Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS).

Method

Members of the European–African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS.

Results

Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30).

Conclusion

Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.
Christian Bioethics:Reflections on a Quarter-Century with the Journal
Authors: Lustig B Andrew
Published: May 2021

This essay reflects on 25 years since Christian Bioethics began publication and, in somewhat autobiographical fashion, engages two core concerns. First, although “non-ecumenism” may often appear a pretext for contention and division, I suggest that a respectful non-ecumenism may provide the opportunity for dialogue and the occasion for employing certain tools from religious studies. Second, although many are skeptical about the possibilities of identifying a “common morality,” a defense of that notion provides a plausible explanation for the development of limited consensus on some issues in bioethics.
Rethinking the Public Sphere in an Age of Radical-Right Populism: A Case for Building an Empathetic Public Sphere
Authors: Korstenbroek Timo
Published: May 2021

With right-wing populist movements gaining ever more traction worldwide, great attention is paid to addressing their exclusionary rhetoric. In this article, I focus on the question how to deal with these radical-right sentiments in our public debates. Believing that both exclusion and inclusion of right-wing populist voices wield counter-productive effects, I juxtapose Habermas’s public sphere theory to Mouffe’s model of agonistic pluralism and posit that both are ultimately insufficient to tackle the populist danger, albeit for different reasons. However, by synthesizing Mouffe’s model with the ideas of Zygmunt Bauman and Iris Marion Young, I introduce the concept of an empathetic public sphere as a model for creating minimal common grounds between right-wing populist “selves” and the “others” they oppose. Finally, I then move this normative model into the realm of media and communication studies and assess how empathetic storytelling might be given shape in today’s fragmented media ecology.
ReMeDy: a platform for integrating and sharing published stem cell research data with a focus on iPSC trials
Authors: Borziak Kirill , Parvanova Irena , Finkelstein Joseph
Published: May 2021

Recent regenerative medicine studies have emphasized the need for increased standardization, harmonization and sharing of information related to stem cell product characterization, to help drive these innovative interventions toward public availability and to increase collaboration in the scientific community. Although numerous attempts and numerous databases have been made to manage these data, a platform that incorporates all the heterogeneous data collected from stem cell projects into a harmonized project-based framework is still lacking. The aim of the database, which is described in this study, is to provide an intelligent informatics solution that integrates comprehensive characterization of diverse stem cell product characteristics with research subject and project outcome information. In the resulting platform, heterogeneous data are validated using predefined ontologies and stored in a relational database, to ensure data quality and ease of access. Testing was performed using 51 published, publically available induced pluripotent stem cell projects conducted in clinical, preclinical and in-vitro evaluations. Future aims of this project include further increasing the database size to include all published stem cell trials and develop additional data visualization tools to improve usability. Our testing demonstrated the robustness of the proposed platform, by seamlessly harmonizing diverse common data elements, and the potential of this platform for driving knowledge generation from the aggregation and harmonization of these diverse data.

Database URL

https://remedy.mssm.edu/
P325 Real-World Effectiveness And Safety Of Ustekinumab In Patients With Ulcerative Colitis: A Multi-Centre Study
Authors: Parakkal D , Johnson A , Fenster M , Ramos G , Zulqarnain M , Ullman T , Huang L , Gutierrez A , Bruss A , Ungaro R , Cohen B , Gaurav S , Anish P , Sasankan P , Costable N , Pekow J , Wang W , Rubin D , Ciorba M , Beniwal-Patel P , Loftus E , Yarur A
Published: May 2021

Background

Pivotal trials have shown that ustekinumab (UST) is effective in ulcerative colitis (UC). However, the population included in these trials do not always represent the cohort of patients treated in the “real world”. In this study, we aimed to describe the effectiveness and safety of UST in a clinical cohort of patients with UC

Methods

We performed a multi-center cohort study and included patients with active UC starting UST. Variables collected included demographics, previous and current UC medications, disease activity (measured using partial and endoscopic Mayo score [PMS and EMS]) at 8 weeks, 6 months and end of follow-up. We also abstracted UST drug level and anti-UST antibodies (AUA), albumin and C-reactive protein levels. Primary outcomes were clinical response at week 8 defined as a reduction of 3 points in the PMS or PMS<2. Secondary outcomes were clinical remission defined as a PMS <2 and endoscopic remission defined as a MES ≤1, and the development of an adverse event (AE) attributed to UST.

Results

Ninety-five patients were included with a median age of 42 years (IQR:32-57) and 53 (56%) were female. Median follow-up was 5 months (IQR:2.2-7.4). Only 4 (4.3%) were naïve to biologics or tofacitinib and 62 (66%) had previous exposure to at least 2 other biologics. No variables were found to be associated with response at week 8 (Figure 2). Those patients who responded at week 8 had higher median albumin levels vs those who did not (median of 4.4 [IQR: 4.1-4.6] vs 4.1 g/dL [IQR:3.8-4.3]; p=0.02). There were no differences in baseline CRP levels (1mg/dL [IQR:0.6-2.8] vs 0.6 mg/dL [0.3-1.5]; p=0.06). Among the 33 patients who had follow-up endoscopic assessment, 7 (21.2%) had achieved endoscopic remission and 4 (12%) achieved histologic remission. Median UST level was 4.1 mcg/ml (IQR:2.5-5.1) and no patients had detectable AUA. Five patients underwent colectomy (5.3%). Only 6 patients (6.6%) presented with an AE (all minor that included, rash, headaches, arthralgias and infection).

Conclusion

In a population enriched with refractory UC, UST was well tolerated and induce response and remission in a significant number of patients. The rate of response was lower in obese patients and those with extensive colitis but was not associated with previous exposure to biologics and/or tofacitinib. Larger studies with a longer follow-up are warranted.

Figure 1: Rates of clinical response and remission in patients with UC receiving ustekinumab

Figure 2: Association between several baseline characteristics and response to ustekinumab in UC
Case report on the importance of longitudinal analysis of left ventricular end-systolic volume, rather than ejection fraction, in a heart transplant patient
Authors: Kerkhof Peter L M , Heyndrickx Guy R
Published: May 2021

Background

Sequential determinations of left ventricular (LV) volume constitute a cornerstone in the mechanical performance evaluation of any heart transplant (HTX) patient. A comprehensive analysis of volumetric data offers unique insight into adaptation and pathophysiology.

Case summary

With a focus on eight sequential biplane angiocardiographic LV end-systolic volume (ESV) determinations, we evaluate the clinical course of a male patient following HTX (female donor) at the age of 61 years. This former smoker had a history of chronic obstructive pulmonary disease, hypertension, and hypercholesterolaemia refractory to treatment, and presented with multivessel coronary artery disease. The later course was complicated by pulmonary hypertension, an abdominal aortic aneurysm, and secondary chronic kidney disease. After an additional episode of pulmonary embolism, the patient died at the age of 79. At one point, the ESV was > 700% higher than the starting value, and actually by far exceeded the relative change of any other volume-based metric evaluated, including ejection fraction (EF).

Discussion

The longitudinal study of LV volumetric data in HTX patients offers a unique window to the pathophysiology of remodelling and sex-specific adaptation processes. The present case documents that proper analysis of serial findings form a rich source of clinically relevant information regarding disease progression. End-systolic volume is the primary indicator, in contrast to the popular metric EF. This finding is supported by population-based studies reported in the literature. We conclude that comprehensive analysis of volumetric data, particularly ESV, contributes to personalized medicine and enhances insight into LV (reverse) remodelling, while also informing about prognosis.
The softer they fall: a natural experiment examining the health effects of job loss before and after Fornero’s unemployment benefit reforms in Italy
Authors: Koltai Jonathan , Varchetta Francesco Maria , McKee Martin , Stuckler David
Published: May 2021

Background

Job loss is a well-established social determinant of health. Recent research has taken an ‘institutional turn’, asking whether unemployment support could buffer the health consequences of job loss. Here, we exploit a quasi-natural experiment based on the Fornero reforms in Italy, which increased wage replacement rates from 60% to 75% on 1 January 2013.

Methods

We employed difference-in-difference models using longitudinal data covering 202 incidents of job loss from the EU-Survey on Income and Living Conditions to quantify the impact of job loss on changes in self-reported health prior to and after the Fornero reforms (2011–14).

Results

Job loss pre-Fornero was associated with health declines −0.342 [95% confidence interval (CI): −0.588 to −0.096] but did not significantly influence health post-Fornero 0.031 (95% CI: −0.101 to 0.164). The difference-in-difference estimate was 0.373 (95% CI: 0.107–0.639), or a −0.51 standard deviation in self-reported health, consistent with the buffering hypothesis. To put the magnitude of this estimate in perspective, the incidence of a chronic illness, such as diabetes, results in a similar magnitude decline in self-reported health.

Conclusions

Our analysis contributes to a growing body of evidence that the impact of job loss on health depends critically on the strength of social protection systems and, in some cases, could be eliminated completely.
Synthetic biology approaches to actinomycete strain improvement
Authors: Breitling Rainer , Avbelj Martina , Bilyk Oksana , Carratore Francesco Del , Filisetti Alessandro , Hanko Erik K R , Iorio Marianna , Redondo Rosario Pérez , Reyes Fernando , Rudden Michelle , Severi Emmanuele , Slemc Lucija , Schmidt Kamila , Whittall Dominic R , Donadio Stefano , García Antonio Rodríguez , Genilloud Olga , Kosec Gregor , De Lucrezia Davide , Petković Hrvoje , Thomas Gavin , Takano Eriko
Published: May 2021

Their biochemical versatility and biotechnological importance make actinomycete bacteria attractive targets for ambitious genetic engineering using the toolkit of synthetic biology. But their complex biology also poses unique challenges. This mini review discusses some of the recent advances in synthetic biology approaches from an actinomycete perspective and presents examples of their application to the rational improvement of industrially relevant strains.
A cross-species approach for the identification of Drosophila male sterility genes
Authors: Ibaraki Kimihide , Nakatsuka Mihoko , Ohsako Takashi , Watanabe Masahide , Miyazaki Yu , Shirakami Machi , Karr Timothy L , Sanuki Rikako , Tomaru Masatoshi , Takano-Shimizu-Kouno Toshiyuki
Published: May 2021

Male reproduction encompasses many essential cellular processes and interactions. As a focal point for these events, sperm offer opportunities for advancing our understanding of sexual reproduction at multiple levels during development. Using male sterility genes identified in human, mouse, and fruit fly databases as a starting point, 103 Drosophila melanogaster genes were screened for their association with male sterility by tissue-specific RNAi knockdown and CRISPR/Cas9-mediated mutagenesis. This list included 56 genes associated with male infertility in the human databases, but not found in the Drosophila database, resulting in the discovery of 63 new genes associated with male fertility in Drosophila. The phenotypes identified were categorized into six distinct classes affecting sperm development. Interestingly, the second largest class (Class VI) caused sterility despite apparently normal testis and sperm morphology suggesting that these proteins may have functions in the mature sperm following spermatogenesis. We focused on one such gene, Rack 1, and found that it plays an important role in two developmental periods, in early germline cells or germline stem cells and in spermatogenic cells or sperm. Taken together, many genes are yet to be identified and their role in male reproduction, especially after ejaculation, remains to be elucidated in Drosophila, where a wealth of data from human and other model organisms would be useful.
Abortion quality of care from the client perspective: a qualitative study in India and Kenya
Authors: Baum Sarah E , Wilkins Rebecca , Wachira Muthoni , Gupta Deepesh , Dupte Shamala , Ngugi Peter , Makleff Shelly
Published: May 2021

Quality healthcare is a key part of people’s right to health and dignity, yet access to high-quality care can be limited by legal, social and economic contexts. There is limited consensus on what domains constitute quality in abortion care and the opinions of people seeking abortion have little representation in current abortion quality measures. In this qualitative study, we conducted 45 interviews with abortion clients in Mumbai, India, and in Eldoret and Thika, Kenya, to assess experiences with abortion care, definitions of quality and priorities for high-quality abortion care. Among the many aspects of care that mattered to clients, the client–provider relationships emerged as essential. Clients prioritized being treated with kindness, respect and dignity; receiving information and counselling that was personalized to their individual situation and reassurance and support from their provider throughout the entire abortion process, including follow-up after the abortion. Many clients also noted the importance of skilled providers and appropriate care. There were similarities across the two country contexts, yet there were some differences in how clients defined high-quality care; therefore, specific political and cultural influences must be considered when implementing measurement and improving person-centred quality of care. These domains, particularly interpersonal interactions, should be prioritized in India and Kenya when health systems, facilities and providers design person-centred measures for quality in abortion care.
‘Fitting in the pharmacist’ – a qualitative analysis of the perceived relationship between community pharmacists and older adults with complex care needs
Authors: Davenport Huyer Larkin , Desveaux Laura , Nakhla Nardine , Maxwell Colleen , Tadrous Mina
Published: May 2021

Objectives

To explore the current perceived relationship between older adults with varying levels of frailty and healthcare needs and community pharmacists.

Methods

This qualitative study conducted a thematic analysis of focus groups with older adults and older adult caregivers and community pharmacist participants. Participants were recruited following a maximum variation sampling technique. Verbatim transcripts were inductively coded using NVivo to develop key findings.

Key findings

Four major themes emerged: (i) Pharmacy Landscape, (ii) Prescription and Non-Prescription Drug Safety, (iii) Patient–Pharmacist Relationship and (iv) Recommendations for Pharmacy Practice. Themes demonstrate three key findings: (1) older adults approach drug information with a key focus on safety and cost of both prescription and non-prescription drugs, (2) there is a demonstrated opportunity, recognized by older adults and practitioners, for community pharmacists to expand their role in the care of older adults, (3) community pharmacists are able, interested and/or have already incorporated frailty assessments into their practice to better support their care of the older adult population with varying levels of frailty.

Conclusions

The results demonstrate a reason for the community pharmacist role to shift. The unique knowledge and skills of community pharmacists, coupled with their accessibility and strong patient–clinician relationship, have the potential to better support older adults with varying levels of frailty.
H
1-stability of the L2-projection onto finite element spaces on adaptively refined quadrilateral meshes
Authors: Ali Mazen , Funken Stefan A , Schmidt Anja
Published: May 2021

The $L^2$-orthogonal projection $ {\varPi }_h:L^2(\varOmega )\rightarrow {\mathbb{V}}_h$ onto a finite element (FE) space $ {\mathbb{V}}_h$ is called $H^1$-stable iff $ \|{ {\varPi }_h u}\|_{H^{1}}(\varOmega )\leq C\|{u}\|_{H^{1}}(\varOmega ) $ for any $u\in H^1(\varOmega )$ with a positive constant $C\neq C(h)$ independent of the mesh size $h>0$. Stability of this projection in the $H^1$-norm is an important component in the numerical analysis of FE methods, and it has been extensively studied before for triangular meshes in two dimensions and tetrahedral meshes in three dimensions. In this work, we analyse $H^1$-stability of adaptively refined quadrilateral meshes in two dimensions. We show that the refinement strategies Q-RG and Q-RB, introduced originally in Bank et al. (1983, Some refinement algorithms and data structures for regular local mesh refinement. Sci. Comput., 1, 3–17) and Kobbelt (1996, Interpolatory subdivision on open quadrilateral nets with arbitrary topology. Comput. Graph Forum, 15, 409–420), are $H^1$-stable for FE spaces of polynomial degree $p=2,\ldots ,9$.
Occupation, Sight, Landscape: Visibility and the Normalization of Israeli Settlements
Authors: Zahora Jakub
Published: May 2021

This article contributes toward the understanding of social and political mechanisms that work to normalize and naturalize contested political conditions on the part of privileged segments of the public. I engage these issues via an ethnographic study of Israel's so-called non-ideological settlements in the occupied West Bank, which attract Israelis due to socioeconomic advantages rather than a nationalistic and/or religious appeal. Nonetheless, the settlers’ suburban experiences are in stark contrast to the geopolitical status of their communities as well as the local and international resistance they generate. I draw empirically on interviews and observations conducted in the settlement of Ariel to make sense of this dynamic. Utilizing insights from critical investigations of visuality and landscape, I argue that the normalization of everyday life in the settlements is achieved through the operation of a particular scopic regime linked to the landscape formations in the West Bank. Employing these concepts to investigate the everyday politics of seeing, I show how they channel the settlers’ sight in a way that makes the Israeli rule seem uncontested, naturalized, and even aesthetic in three registers: the depth of visual field, the surroundings, and the people who inhabit the settlements’ landscape.
Feasibility of capturing real-world data from health information technology systems at multiple centers to assess cardiac ablation device outcomes: A fit-for-purpose informatics analysis report
Authors: Jiang Guoqian , Dhruva Sanket S , Chen Jiajing , Schulz Wade L , Doshi Amit A , Noseworthy Peter A , Zhang Shumin , Yu Yue , Patrick Young H , Brandt Eric , Ervin Keondae R , Shah Nilay D , Ross Joseph S , Coplan Paul , Drozda Joseph P
Published: May 2021

Objective

The study sought to conduct an informatics analysis on the National Evaluation System for Health Technology Coordinating Center test case of cardiac ablation catheters and to demonstrate the role of informatics approaches in the feasibility assessment of capturing real-world data using unique device identifiers (UDIs) that are fit for purpose for label extensions for 2 cardiac ablation catheters from the electronic health records and other health information technology systems in a multicenter evaluation.

Materials and Methods

We focused on data capture and transformation and data quality maturity model specified in the National Evaluation System for Health Technology Coordinating Center data quality framework. The informatics analysis included 4 elements: the use of UDIs for identifying device exposure data, the use of standardized codes for defining computable phenotypes, the use of natural language processing for capturing unstructured data elements from clinical data systems, and the use of common data models for standardizing data collection and analyses.

Results

We found that, with the UDI implementation at 3 health systems, the target device exposure data could be effectively identified, particularly for brand-specific devices. Computable phenotypes for study outcomes could be defined using codes; however, ablation registries, natural language processing tools, and chart reviews were required for validating data quality of the phenotypes. The common data model implementation status varied across sites. The maturity level of the key informatics technologies was highly aligned with the data quality maturity model.

Conclusions

We demonstrated that the informatics approaches can be feasibly used to capture safety and effectiveness outcomes in real-world data for use in medical device studies supporting label extensions.
Lift the Ban? Initial Employment Restrictions and Refugee Labour Market Outcomes
Authors: Fasani Francesco , Frattini Tommaso , Minale Luigi
Published: May 2021

This paper investigates the medium- to long-term effects on refugee labour market outcomes of the temporary employment bans being imposed on asylum seekers in many countries. Using a newly collected data set on employment restrictions together with individual data for refugees entering European countries between 1985 and 2012, our empirical strategy exploits the geographical and temporal variation in employment bans generated by their staggered introduction and removal coupled with frequent changes at the intensive margin. We find that exposure to a ban at arrival reduces refugee employment probability in post-ban years by 15%, an impact driven primarily by lower labour market participation. These effects are not mechanical, increase non-linearly in ban length, and last up to 10 years post arrival. The detrimental effects of employment bans are concentrated among less educated refugees, translate into lower occupational quality, and seem not to be driven by selective migration. Our causal estimates are robust to several identification tests accounting for the potential endogeneity of employment ban policies, including placebo analysis of non-refugee migrants and an instrumental variable strategy. We estimate a €37.6 billion output loss from the bans imposed on asylum seekers who arrived in Europe during the so-called 2015 refugee crisis.