bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Gluten-Free Diet on Thyroid Autoimmunity in Drug-Naïve Women with Hashimoto’s Thyroiditis: A Pilot Study
Authors: Krysiak Robert , Szkróbka Witold , Okopień Bogusław
Published: July 2018

Background Autoimmune thyroid disease is often accompanied by celiac disease.

Objective The purpose of this study was to investigate whether a gluten-free diet affects thyroid autoimmunity, hypothalamic-pituitary-thyroid axis activity and thyroid function tests in women with Hashimoto’s thyroiditis and incidentally found positive anti-tissue transglutaminase antibodies.

Methods The study included 34 women with autoimmune thyroiditis divided into two group. The patients belonging to the first one (group A, n=16) complied with the gluten-free diet for 6 months, while the remaining patients (group B, n=18) remained without any dietary treatment. Serum titers of thyroid peroxidase and thyroglobulin antibodies, as well as serum levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D were measured at the beginning of the study and 6 months later. Based on thyrotropin and free thyroid hormone levels, Jostel’s thyrotropin index, the SPINA-GT index and the SPINA-GD index were calculated.

Results All patients completed the study protocol. In group B, serum thyrotropin and free thyroid hormones levels, serum 25-hydroxyvitamin D levels as well as the calculated indices remained at the similar levels. The gluten-free diet reduced thyroid antibody titers, as well as slightly increased 25-hydroxyvitamin D levels and the SPINA-GT index. In group A, the impact on TPOAb and TgAb titers correlated with the changes in the SPINA-GT index, whereas the impact on TPOAb with the changes in 25-hydroxyvitamin D levels.

Conclusions The obtained results suggest that the gluten-free diet may bring clinical benefits to women with autoimmune thyroid disease.
Palladium-Catalyzed Decarboxylative Benzylation of Acetylides and Enolates
Authors: Tunge Jon , Torregrosa Robert , Mendis Shehani , Davies Alex
Published: July 2018

Benzylic alkylation of enolates and acetylides has been achieved through the use of a decarboxylative benzylation strategy. Previous research in this area is often limited by the need for extended conjugation in the electrophiles that are coupled. Herein, we report that the use of 1,1'-bis(diphenylphosphino)ferrocene (dppf) ligand allows the coupling of simple benzyl electrophiles with enolates, while the use of XPhos ligand promotes the decarboxylative couplings of propiolates.
Chronic Alcoholism Decreases Polyunsaturated Fatty Acid Levels in Human Plasma, Erythrocytes, and Platelets – Influence of Chronic Liver Disease
Authors: Pita María-Luisa , Rubio José-María , Murillo María-Luisa , Carreras Olimpia , Delgado Mariá-José
Published: July 2018

The effect of chronic ethanol ingestion on fatty acid composition of plasma, erythrocyte and platelet phospholipids and on plasma 6-keto-PGF1α was studied. Two groups of alcoholic subjects, one of them with chronic liver disease, were studied and compared to a control group of healthy subjects. Linoleic acid was not affected by alcoholism but its larger metabolites arachidonic acid (20:4n6) and docosatetraenoic acid (22: 4n6) tended to be lower in erythrocytes and platelets of both groups of alcoholic patients; the decrease was more marked in the presence of chronic liver disease. Docosahexaenoic acid (22:6n3) was markedly decreased in plasma, erythrocytes and platelets obtained from alcoholic patients with chronic liver disease. Plasma levels of 6-keto-PGF1α, a metabolite of prostacyclin (PGI2), remained unchanged. We conclude that chronic ethanol ingestion induces important changes in long-chain polyunsaturated fatty acids, mainly in platelets, and that these changes are exacerbated when patients suffer from chronic liver disease.
Factor VII Toyama (Thr 359 Met): A Homozygous Missense Mutation Causing Severe Type I Deficiency
Authors: Ozawa Tetsuo , Niiya Kenji , Higuchi Wataru , Sakuragawa Nobuo
Published: July 2018

We performed a DNA analysis on a patient with severe type I factor VII deficiency by the polymerase chain reaction amplification and a direct DNA sequencing method. The proband was a 66-year-old Japanese woman who had recurrent episodes of excessive bleeding after dental extraction. The functional and antigenic levels of plasma factor VII markedly reduced to 1.6% and 2% of normal, respectively. However, she had no serious symptoms such as intracranial or intraarticular hemorrhage. The analysis revealed that the patient was homozygous for a missense mutation, Thr (ACG) to Met (ATG) at codon 359 in the catalytic domain. Her deceased parents were first cousins, and their consanguineous marriage presumably resulted in the homozygosity in her.

This patient was the first case of homozygote for the Thr359Met mutation, though heterozygotes for the mutation were previously found in an Italian family.
Electrospray Ionisation Analysis of Human Fibrinogen
Authors: Brennan Stephen O
Published: July 2018

Fibrinogen, a 340 kDa glycoprotein, was purified from human plasma, separated into its constituent polypeptide chains and analyzed by electrospray ionization mass spectrometry. Six individual plasmas were examined, and whilst the Aα chain appeared homogeneous, the Bβ and γ chains were heterogeneous with the predominant form of each lacking a single sialic acid residue. The mean molecular masses of the dominant γ and Bβ isoforms were 48,366 and 54,200 Da with standard deviations of 10 and 12 Da respectively compared to predictions, based on amino acid and carbohydrate sequences, of 48,368 and 54,213 Da. The mean mass of the Aa chain was 66,196 Da but this showed significantly more variation with a standard deviation of 64 Da. This probably reflects genetic and/or post-translational differences, since there is non-stoichiometric phosphorylation at Ser 3 and 345 and the expected residue weight of the non-phosphorylated chain is 66,132 Da.

After treatment with thrombin the fibrin β chain showed a decrease in mass of 1542 Da in good agreement with the expected decrease of 1535 Da resulting from loss of the B peptide. Loss of the A peptide from the α chain resulted in a decrease of 1546 Da compared to an expected loss of 1519 Da for non-phosphorylated A peptide. On prolonged thrombin incubations factor XIII induced γ-γ dimers were observed at 96,896 Da.
The Feasibility of a Modified Exclusive Endoscopic Transcanal Transpromontorial Approach for Vestibular Schwannomas
Authors: Moon In , Cha Dongchul , Nam Sung-Il , Lee Hyun-Jin , Choi Jae
Published: July 2018

Objective We evaluated the feasibility of an exclusive endoscopic transcanal transpromontorial approach (EETTA) for the treatment of small vestibular schwannomas (VSs) limited to the internal auditory canal (IAC), and introduced a modification without external auditory canal closure.

Methods Between June 2016 and June 2017, seven patients with VS underwent surgery using a modified EETTA. Treatment outcomes, including efficacy of tumor resection, preservation of function, operation time, and quality of life (QOL), were evaluated.

Results The patients preoperatively exhibited Koos Grade I/II tumors and severe-to-profound hearing loss. Gross total resection was accomplished in all cases. There were no major complications, and all patients exhibited normal facial nerve function immediately after surgery. The mean follow-up period was 12.9 months. The operation time (average 196.3 ± 64.9 minutes) and hospitalization period (average 7.4 ± 1.0 days) were favorable. Short Form-36 scores for QOL showed unremarkable results compared with previous reports.

Conclusions The modified EETTA was effective in the removal of VSs in the IAC. It can be an alternative surgical option for small VSs.
Combined David and Frozen Elephant Trunk Procedure in Acute Aortic Dissection
Authors: Goebel Nora , Nagib Ragi , Salehi-Gilani Schahriar , Ahad Samir , Albert Marc , Ursulescu Adrian , Franke Ulrich F.W.
Published: July 2018

Background Valve sparing aortic root repair by reimplantation (David procedure) is an established technique in acute aortic dissection Stanford type A involving the aortic root. In DeBakey type I dissection, aortic arch replacement using the frozen elephant trunk (FET) was introduced to promote aortic remodeling of the downstream aorta. The combination of these two complex procedures represents a challenging surgical strategy and was considered too risky so far.

Methods All patients with acute aortic dissection DeBakey type I undergoing valve sparing aortic root repair by reimplantation technique of David combined with extended aortic repair using the FET at our center between October 2009 and December 2016 were evaluated. Outcomes are compared with patients who underwent prosthetic aortic root replacement and FET for aortic dissection in the same timeframe.

Results A total of 28 patients received combined David and FET procedure, while 20 patients received prosthetic aortic root replacement and FET procedure. Thirty-day mortality was 10.7% (n = 3) for the David group and 20% (n = 4) for the root replacement group (p = 0.43). Postoperative echocardiographic control revealed an excellent aortic valve function with regurgitation grade 0° or maximum grade I° and a mean gradient of 4.3 ± 2.1 mm Hg in all patients in the David group versus 7.2 ± 2.4 mm Hg in the aortic root replacement group, p = 0.003. Computed tomography angiography scan showed positive aortic remodeling in all but three patients (91.9%). Mid-term follow-up survival was 82.1% in the David group and 68.4% in the root replacement group, p = 0.28. There was no need for reintervention at the root or descending aorta.

Conclusion Simultaneous application of the David and FET procedure in patients with acute aortic dissection is safe and feasible in experienced hands as compared with standard aortic root replacement plus FET. The mid-term outcomes are encouraging and noninferior to conventional surgery results.
Excessive Salivation as a Hidden Comorbidity of Basal Ganglia Germ Cell Tumor
Authors: Kobayashi Kenichiro , Suehiro Minoru , Maihara Toshiro , Usami Ikuya , Heike Toshio
Published: July 2018

The progression of basal ganglia germ cell tumor (BGGCT) is slow and insidious, and the diagnosis is often delayed. We report here an 11-year-old boy with BGGCT associated with psychomotor deterioration and excessive salivation. Serial salivary gland scintigraphy and single photon emission computed tomography suggested that the dysregulation of basal ganglia to cortical circuitry accounts for the neurological comorbidity associated with BGGCT. We also found that topical scopolamine patches are safe and effective to suppress excessive salivation.

Clinical Trial Registration: No.
Barriers to Postpartum Glucose Testing in Women with Gestational Diabetes Mellitus
Authors: Has Phinnara , Kanno Lindsey , Sullivan Adam , Clark Melissa , Werner Erika
Published: July 2018

Objective To identify barriers to postpartum glucose testing in women with a history of gestational diabetes mellitus (GDM).

Materials and Methods This is a prospective cohort study of 300 women with GDM who completed questionnaires on socioeconomic barriers and validated instruments to measure trust in their clinician and health agency. At 12 weeks' postpartum, women were recontacted and postpartum records were collected. Women who completed glucose testing between 4 and 12 weeks' postpartum were compared with women who did not with regard to modifiable and nonmodifiable barriers to care.

Results Of the 373 women approached, 300 (80%) consented to participate, completed surveys on postpartum day 2, and had records retrieved at 12 weeks' postpartum. Validated instruments used showed internal consistency (Cronbach's α > 0.6). Only 126 (42%) of the participants completed postpartum glucose testing, and these women were more likely to have reliable transportation, private insurance, college degrees, and higher annual household incomes (p < 0.05). Postpartum glucose testing was also associated with trust in clinicians (p = 0.01) but not health agency (p = 0.66). The association between trust and postpartum glucose testing persisted after adjusting for nonmodifiable barriers.

Conclusion Maximizing trust in clinicians should be a focus of prenatal GDM care to maximize the likelihood of postpartum glucose testing.
Warsaw breakage syndrome DDX11 helicase acts jointly with RAD17 in the repair of bulky lesions and replication through abasic sites
Authors: Abe Takuya , Ooka Masato , Kawasumi Ryotaro , Miyata Keiji , Takata Minoru , Hirota Kouji , Branzei Dana
Published: July 2018

Significance

Warsaw breakage syndrome, a developmental disorder caused by mutations in the conserved DDX11/ChlR1 DNA helicase, shows features of genome instability partly overlapping with those of Fanconi anemia (FA). Here, using avian cellular models of DDX11 deficiency, we find that DDX11 functions as backup to the FA pathway and facilitates, jointly with the checkpoint clamp 9-1-1, a homologous recombination pathway of DNA bulky-lesion repair that does not affect replication fork speed and stalled fork stability. DDX11 also promotes diversification of the immunoglobulin-variable gene locus by facilitating hypermutation and gene conversion at programmed abasic sites that constitute endogenous replication blocks. The results suggest commonality between postreplicative gap filling and replication through abasic sites and pinpoint DDX11 as a critical player in both these processes.
p53-inducible DPYSL4 associates with mitochondrial supercomplexes and regulates energy metabolism in adipocytes and cancer cells
Authors: Nagano Hidekazu , Hashimoto Naoko , Nakayama Akitoshi , Suzuki Sawako , Miyabayashi Yui , Yamato Azusa , Higuchi Seiichiro , Fujimoto Masanori , Sakuma Ikki , Beppu Minako , Yokoyama Masataka , Suzuki Yutaka , Sugano Sumio , Ikeda Kazuhiro , Tatsuno Ichiro , Manabe Ichiro , Yokote Koutaro , Inoue Satoshi , Tanaka Tomoaki
Published: July 2018

Significance

We herein performed RNA sequencing to show that DPYSL4 is a p53-inducible regulator of energy metabolism in both cancer cells and normal cells, such as adipocytes. DPYSL4 was found to localize in both cytosol and mitochondria, particularly in associations with mitochondrial supercomplexes, providing a potential mechanism for its regulation of OXPHOS and cellular energy supply. Furthermore, DPYSL4 expression suppressed tumor growth and metastasis in vivo. Together, these results suggest a potential link between p53-inducible DPYSL4 and the pathophysiology of cancer and metabolic disorders, possibly via its energy-regulating function.
Vladimir Voevodsky—An appreciation
Authors: Levine Marc
Published: July 2018

We give a brief résumé of some of the works of the late Vladimir Voevodsky.
Multiple determinants and consequences of cohesion fatigue in mammalian cells
Authors: Sapkota Hem , Wasiak Emilia , Daum John R. , Gorbsky Gary J.
Published: July 2018

Cells delayed in metaphase with intact mitotic spindles undergo cohesion fatigue, where sister chromatids separate asynchronously, while cells remain in mitosis. Cohesion fatigue requires release of sister chromatid cohesion. However, the pathways that breach sister chromatid cohesion during cohesion fatigue remain unknown. Using moderate-salt buffers to remove loosely bound chromatin cohesin, we show that “cohesive” cohesin is not released during chromatid separation during cohesion fatigue. Using a regulated protein heterodimerization system to lock different cohesin ring interfaces at specific times in mitosis, we show that the Wapl-mediated pathway of cohesin release is not required for cohesion fatigue. By manipulating microtubule stability and cohesin complex integrity in cell lines with varying sensitivity to cohesion fatigue, we show that rates of cohesion fatigue reflect a dynamic balance between spindle pulling forces and resistance to separation by interchromatid cohesion. Finally, while massive separation of chromatids in cohesion fatigue likely produces inviable cell progeny, we find that short metaphase delays, leading to partial chromatid separation, predispose cells to chromosome missegregation. Thus, complete separation of one or a few chromosomes and/or partial separation of sister chromatids may be an unrecognized but common source of chromosome instability that perpetuates the evolution of malignant cells in cancer.
Association of Either Left Ventricular Hypertrophy or Diastolic Dysfunction With 24-Hour Central and Peripheral Blood Pressure
Authors: Blanch Pedro , Armario Pedro , Oliveras Anna , Fernández-Llama Patricia , Vázquez Susana , Pareja Julia , Álvarez Empar , Calero Francesca , Sierra Cristina , de la Sierra Alejandro
Published: July 2018

BACKGROUND

Central blood pressure (BP) is considered as a better estimator of hypertension-associated risks than peripheral BP. We aimed to evaluate the association of 24-hour central BP, in comparison with 24-hour peripheral BP, with the presence of left ventricular hypertrophy (LVH), or diastolic dysfunction (DD).

METHODS

The cross-sectional study consisted of 208 hypertensive patients, aged 57 ± 12 years, of which 34% were women. Office and 24-hour central and peripheral BP were measured by the oscillometric Mobil-O-Graph device. We performed echocardiography–Doppler measurements to calculate LVH and DD, defined as left atrium volume ≥34 ml/m2 or septal e′ velocity <8 cm/s or lateral e′ velocity <10 cm/s.

RESULTS

Seventy-seven patients (37%) had LVH, and 110 patients (58%) had DD. Systolic and pulse BP estimates (office, 24-hour, daytime, and nighttime) were associated with the presence of LVH or DD, after adjustment for age, gender, and antihypertensive treatment, with higher odds ratios for ambulatory-derived values. The comparison between central and peripheral BP estimates did not reveal a statistically significant superiority of the former neither in multiple regression models with simultaneous adjustments nor in the comparison of areas under receiver-operating curves. Correlation coefficients of BP estimates with left ventricular mass, although numerically higher for central BP, did not significantly differ between central and peripheral BP.

CONCLUSIONS

We have not found a significant better association of 24-hour central over peripheral BP, with hypertensive cardiac alterations, although due to the sample size, these results require further confirmation in order to assess the possible role of routine 24-hour central BP measurement.
Proprioceptive Weighting Ratio for Balance Control in Static Standing Is Reduced in Elderly Patients With Non–Specific Low Back Pain
Authors: Ito Tadashi , Sakai Yoshihito , Morita Yoshifumi , Yamazaki Kazunori , Igarashi Kazuma , Nishio Reiya , Sato Noritaka
Published: July 2018

MINI

Elderly patients older than 65 years were divided into non-specific low back pain (NSLBP) and non-LBP (NLBP) groups. The postural control study of the relative contributions of different proprioceptive signals (relative proprioceptive weighting ratio [RPW]) revealed lower leg proprioceptive decreases (RPW 240 Hz) in NSLBP compared to NLBP.

Study Design.

A cross-sectional, observational study.

Objective.

The aim of this study was to determine a specific proprioceptive control strategy during postural balance in elderly patients with non-specific low back pain (NSLBP) and non-LBP (NLBP).

Summary of Background Data.

Proprioceptive decline is an important risk factor for decreased balance control in elderly patients with NSLBP. The resulting reduction in proprioception in the trunk or lower legs may contribute to a reduction in postural sway. This study aims to determine the specific proprioceptive control strategy used during postural balance in elderly patients with NSLBP and NLBP and to assess whether this strategy is related to proprioceptive decline in NSLBP.

Methods.

Pressure displacement centers were determined in 28 elderly patients with NSLBP and 46 elderly patients with NLBP during upright stances on a balance board without the benefit of vision. Gastrocnemius and lumbar multifidus muscle vibratory stimulations at 30, 60, and 240 Hz, respectively, were applied to evaluate the relative contributions of the different proprioceptive signals (relative proprioceptive weighting ratio, RPW) used in postural control.

Results.

Compared to elderly patients with NLBP, those with NSLBP had a lower RPW at 240 Hz and significantly higher RPW at 30 Hz. A logistic regression analysis showed that RPW at 240 Hz was independently associated with NSLBP after controlling for confounding factors.

Conclusion.

Elderly patients with NSLBP decreased their reliance on ankle strategy (RPW at 240 Hz) and hip strategy (RPW at 30 Hz) proprioceptive signals during balance control. The inability to control hip and ankle strategies indicates a deficit of postural control and is hypothesized to result from proprioceptive impairment. Moreover, elderly patients with NSLBP are at higher risk for lower leg proprioceptive decrease (240 Hz) through the NSLBP exacerbation.

Level of Evidence: 4
Endonasal Approach to Orbital Pathology
Authors: Curragh David S. , Halliday Luke , Selva Dinesh
Published: July 2018

Purpose:

Transnasal endoscopic orbital surgery in an emerging surgical field. The surgical field has expanded from orbital decompression to excision of tumours from the medial orbit and over the last 20 years. As instrumentation has improved, the nature, location and size of tumours being excised has changed.

Methods:

This article discusses the salient surgical considerations when approaching an orbital lesion via a transnasal endoscopic route and reviews the literature.

Results:

An endonasal approach offers a potential space surgeons can utilise to access the orbit, possibly providing additional exposure, illumination and magnification to the medial and apical aspects of selected lesions.

Conclusions:

An endonasal approach may be useful as a sole or adjunctive approach in selected cases of orbital tumour excision.
Minimally Invasive Corneal Neurotization With Acellular Nerve Allograft: Surgical Technique and Clinical Outcomes
Authors: Leyngold Ilya M. , Yen Michael T. , Tian James , Leyngold Mark M. , Vora Gargi K. , Weller Christopher
Published: July 2018

Purpose:

To describe a minimally invasive surgical technique and its clinical outcomes with the use of acellular nerve allograft to re-establish corneal sensibility in patients with neurotrophic keratopathy.

Methods:

Acellular nerve allograft was coapted to an intact supraorbital, supratrochlear, or infraorbital nerve and transferred to the affected eye. Donor nerve pedicles were isolated through a transpalpebral or transconjunctival approach. Retrospective evaluation of preoperative and postoperative corneal sensibility, ocular surface, and best-corrected visual acuity was performed in all patients. Mean follow-up period was 6 months (range: 3–10 months).

Results:

Corneal neurotization with acellular nerve allograft was successfully performed in 7 patients with restoration of corneal sensibility and corneal epithelial integrity. In vivo confocal microscopy demonstrated increased nerve density in corneal stroma at 4 months after surgery.

Conclusions:

The use of acellular nerve allograft allows for a minimally invasive approach to successful corneal neurotization.
Anatomy and Physical Examination of the Shoulder
Authors: Bakhsh Wajeeh , Nicandri Gregg
Published: July 2018

The shoulder is a complex joint, with a wide range of motion and functional demands. An understanding of the intricate network of bony, ligamentous, muscular, and neurovascular anatomy is required in order to properly identify and diagnose shoulder pathology. There exist many articulations, unique structural features, and anatomic relationships that play a role in shoulder function, and therefore, dysfunction and injury. Evaluation of a patient with shoulder complaints is largely reliant upon physical exam. As with any exam, the basic tenets of inspection, palpation, range of motion, strength, and neurovascular integrity must be followed. However, with the degree of complexity associated with shoulder anatomy, specific exam maneuvers must be utilized to isolate and help differentiate pathologies. Evaluation of rotator cuff injury, shoulder instability, or impingement via exam guides clinical decision-making and informs treatment options.
Rotator Cuff Disease: Treatment Options and Considerations
Authors: Dang Alexis , Davies Michael
Published: July 2018

Rotator cuff disease encompasses a broad spectrum of injury and pathology with an increasing incidence with age. Pain with overhead activity, localizing to the deltoid region, and loss of active range of motion of the shoulder are among the most common presenting symptoms. Treatment options are dependent on the extent of disease and patient symptoms, and may range from physical therapy to surgical repair using a variety of possible techniques. Tear thickness, size, and morphology frequently dictate the repair techniques that are used, such as margin convergence, anterior and posterior interval slides, and mobilization of the rotator interval and supraspinatus with a subscapularis repair. Establishing and maintaining a low-tension repair is important in optimizing tendon healing after surgery. Superior capsule reconstruction is an emerging treatment strategy for massive, otherwise irreparable cuff tears, though more long-term evidence is necessary to fully evaluate this option.
Quality Improvement Bedside Rounding Audits Enhance Protein Provision for Pediatric Patients Receiving Continuous Renal Replacement Therapy*
Authors: Vega Molly Wong , Juarez Marisa , Lee Ji Yeon , Srivaths Poyyapakkam , Williams Eric , Akcan Arikan Ayse
Published: July 2018

Objectives:

Describe quality improvement process improvements in protein delivery of continuous renal replacement therapy initiation.

Design:

Prospective study.

Setting:

PICU and cardiovascular ICU within a quaternary care children’s hospital.

Patients:

PICU and cardiovascular ICU patients receiving continuous renal replacement therapy for greater than 48 hours. Inborn errors of metabolism were excluded.

Interventions:

Plan-Do-Study-Act cycles were initiated. Cycle 1 developed interdisciplinary quality improvement group continuously monitoring nutrition care with thrice weekly bedside safety rounds and protein prescriptions within nephrologist’s notes. Cycle 2 included education to intensivists. Cycle 3 initiated monthly quality improvement meetings reviewing nutritional care goals.

Measurements and Main Results:

Primary outcome was percentage of time patients met protein goals in the first 5 days of continuous renal replacement therapy. Secondary outcome was percentage of time patients met protein goals for duration of continuous renal replacement therapy. Cohort (n = 55) mean age was 8.1 years (sd ± 6.8), 62% male, and 31% malnutrition at baseline. Percent of time meeting protein goals by day 5 was 22%, 33%, and 71% and percent of time meeting protein goals throughout was 35%, 39%, and 75% of groups 1, 2, and 3, respectively. Significant improvement occurred after Plan-Do-Study-Act 3 (group 2 vs group 3; p < 0.01) for primary and secondary outcomes.

Conclusions:

Implementation of an interprofessional quality improvement team significantly decreased number of continuous renal replacement therapy days with unmet protein goals and improved protein delivery.
Therapeutic Responses and Survival Effects of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castrate-Resistant Prostate Cancer
Authors: Kim Yong Joong , Kim Yong-il
Published: July 2018

Purpose

We performed a meta-analysis on the therapeutic effects of prostate-specific membrane antigen (PSMA)–617 labeled with lutetium-177 (177Lu-PSMA-617) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Patients and Methods

The primary outcome was the therapeutic responses after the first cycle of 177Lu-PSMA-617 radioligand therapy. The parameters studied were the pooled proportions of any prostate-specific antigen (PSA) decline and a greater than 50% PSA decline. The secondary outcome was the survival effects after 177Lu-PSMA-617 radioligand therapy. Studied parameters were pooled hazard ratios of the overall survival according to any PSA decline and a greater than 50% PSA decline after the first cycle of 177Lu-PSMA-617 radioligand therapy.

Results

In total, 10 eligible studies with 455 patients were finally included in this meta-analysis. The pooled proportions of any PSA decline was 68.00% (95% confidence interval [CI], 63.55%–72.22%], and those with a greater than 50% PSA decline was 34.45% (95% CI, 30.14%–38.97%). The pooled hazard ratios for the overall survival of any PSA decline was 0.29 (95% CI, 0.21–0.40) with significance (P < 0.00001); however, a greater than 50% PSA decline was 0.82 (95% CI, 0.54–1.25) with no significance (P = 0.39).

Conclusions

We suggest that approximately two-thirds of any PSA decline and one-third of a greater than 50% PSA decline can be expected after the first cycle of 177Lu-PSMA-617 radioligand therapy in patients with mCRPC. Moreover, any PSA decline showed survival prolongation after the first cycle of the 177Lu-PSMA-617 radioligand therapy.
An Incidental Finding of Subcutaneous Hemangioma During 99mTcO4 Salivary Gland Scintigraphy
Authors: Zhao Zhen , Chen Yu , Liu Bin
Published: July 2018

A 43-year-old woman with papillary thyroid cancer prepared for 131I ablation after total thyroidectomy. With a history of type 2 diabetes for 10 years, she recently presented with periodontitis, candidiasis, and mouth dryness. 99mTcO4 scintigraphy was ordered to evaluate function of the salivary glands. The scintigraphy incidentally found a focal 99mTcO4 uptake in the left supraclavicular region. The subsequent neck ultrasonography showed a hypoechoic soft tissue mass with heterogeneous hypervascularity, suggestive of hemangioma.
177Lu-DOTATATE Therapy in Radioiodine-refractory Differentiated Thyroid Cancer
Authors: Roll Wolfgang , Riemann Burkhard , Schäfers Michael , Stegger Lars , Vrachimis Alexis
Published: July 2018

Introduction

Patients with radioiodine-refractory differentiated thyroid cancer (RrDTC) have a rather poor prognosis and are in need of novel treatments. As RrDTCs can in some cases express somatostatin receptors (SSRT), targeting of these receptors by 68Ga/177Lu-DOTATATE could evolve as a novel theranostic option.

Methods

Five RrDTC patients with limited further therapeutic options and documented expression of SSRT using 68Ga-DOTATATE-PET/CT received 2 to 4 cycles of PRRT with 177Lu-DOTATATE. Response to therapy was assessed by thyroglobulin (Tg) and morphological and metabolic criteria based on interim and follow-up 68Ga-DOTATATE-PET/CTs. Analysis was performed on a per-patient basis.

Results

In the post-therapy evaluation, only one out of five patients showed a partial response, whereas three patients had a progressive disease. One patient had discordant findings between stable imaging results albeit rising Tg levels.

Conclusion

In this case study of five patients, 177Lu-DOTATATE therapy showed only heterogeneous response and efficacy in RrDTC patients despite good lesional uptake in pre-therapeutic PET.
Targeted Therapy With Anaplastic Lymphoma Kinase Inhibitor (Alectinib) in Adolescent Metastatic Non–Small Cell Lung Carcinoma
Authors: Usmani Sharjeel , Marafi Fahad , Rasheed Rashid , Al Maraghy Muneera , al Kandari Fareeda
Published: July 2018

Primary lung adenocarcinoma is extremely rare in the pediatric age group. We report an 18-year-old man with non–small cell lung carcinoma stage IV with brain and bone metastatic. Lung biopsy showed expression of PDL1 along with rearrangement of ALK gene at chromosome 2p23. However, neither mutation of ROS1 nor epidermal growth factor receptor overexpression was seen. Second-generation anaplastic lymphoma kinase (ALK) inhibitor (alectinib) is initiated as first line of treatment. After 8 months of treatment with alectinib, 18F-NaF PET/CT demonstrated resolution of bone lesions. The present case show rapid and good response to alectinib in metastatic ALK-positive non–small cell lung carcinoma.
Multiple Subcutaneous Nodules as Initial Presentation of Diffuse Large B-cell Non-Hodgkin Lymphoma (DLBCL) Detected by PET/CT
Authors: Shen Guohua , Kou Ying , Liu Bin , Kuang Anren
Published: July 2018

Subcutaneous tissue as a manifestation of generalized disease is commonly involved in lymphomas. However, only skin involvement without other sites of extracutaneous disease was rarely presented, especially in diffuse large B-cell lymphoma (DLBCL). Herein, we reported an unusual case of primary cutaneous DLBCL, solely presenting with multiple subcutaneous nodules in the abdomen and back, and these nodules showed increased FDG uptake on PET/CT images. PET/CT is very helpful for diagnosing primary cutaneous DLBCL.
Assessing Patient Satisfaction Among Transgender Individuals Seeking Medical Services
Authors: Smith Jesse R. , Washington Arthur Zayne , Morrison Shane D. , Gottlieb Lawrence J.
Published: July 2018

Background

Gender dysphoria is estimated to occur in up to 0.4% of the US population. Gender-confirming surgery (GCS) has been shown to improve the quality of life of transgender patients. However, a dearth of standardized and reliable measures specific to transgender individuals exists to objectively gauge sensitivity and competency among providers caring for these patients.

Methods

A comprehensive literature search of PubMed, MEDLINE, ISI Web of Science, and Cochrane databases using search terms related to provider competency and sensitivity during consultation for GCS was conducted for studies published through December 2017. Data were gathered from the publications that met inclusion criteria.

Results

The total number of articles focusing on transgender persons was 14 of more than 75,000 patient satisfaction–oriented published articles (<0.001%). Only 8 (57%) of the 14 represented original research. After applying the inclusion criteria, only 2 were found to discuss measures of patient satisfaction specific to transgender individuals. Of these 2, none evaluated patient satisfaction specific to the time of surgical consultation.

Conclusions

With increasing awareness and decreasing stigma surrounding transgender issues, it is likely that more transgender individuals will begin to seek GCS. There is a need for patient-reported experience measures specific to transgender individuals in order to appropriately gauge the interactions they experience with their surgeons. However, current instruments are neither standardized nor reliable for transgender patients to gauge provider sensitivity and competency.
Detecting clinically actionable variants in the 3’ exons of PMS2 via a reflex workflow based on equivalent hybrid capture of the gene and its pseudogene
Authors: Gould Genevieve M. , Grauman Peter V. , Theilmann Mark R. , Spurka Lindsay , Wang Irving E. , Melroy Laura M. , Chin Robert G. , Hite Dustin H. , Chu Clement S. , Maguire Jared R. , Hogan Gregory J. , Muzzey Dale
Published: July 2018

Background

Hereditary cancer screening (HCS) for germline variants in the 3’ exons of PMS2, a mismatch repair gene implicated in Lynch syndrome, is technically challenging due to homology with its pseudogene PMS2CL. Sequences of PMS2 and PMS2CL are so similar that next-generation sequencing (NGS) of short fragments—common practice in multigene HCS panels—may identify the presence of a variant but fail to disambiguate whether its origin is the gene or the pseudogene. Molecular approaches utilizing longer DNA fragments, such as long-range PCR (LR-PCR), can definitively localize variants in PMS2, yet applying such testing to all samples can have logistical and economic drawbacks.

Methods

To address these drawbacks, we propose and characterize a reflex workflow for variant discovery in the 3’ exons of PMS2. We cataloged the natural variation in PMS2 and PMS2CL in 707 samples and designed hybrid-capture probes to enrich the gene and pseudogene with equal efficiency. For PMS2 exon 11, NGS reads were aligned, filtered using gene-specific variants, and subject to standard diploid variant calling. For PMS2 exons 12-15, the NGS reads were permissively aligned to PMS2, and variant calling was performed with the expectation of observing four alleles (i.e., tetraploid calling). In this reflex workflow, short-read NGS identifies potentially reportable variants that are then subject to disambiguation via LR-PCR-based testing.

Results

Applying short-read NGS screening to 299 HCS samples and cell lines demonstrated >99% analytical sensitivity and >99% analytical specificity for single-nucleotide variants (SNVs) and short insertions and deletions (indels), as well as >96% analytical sensitivity and >99% analytical specificity for copy-number variants. Importantly, 92% of samples had resolved genotypes from short-read NGS alone, with the remaining 8% requiring LR-PCR reflex.

Conclusion

Our reflex workflow mitigates the challenges of screening in PMS2 and serves as a guide for clinical laboratories performing multigene HCS. To facilitate future exploration and testing of PMS2 variants, we share the raw and processed LR-PCR data from commercially available cell lines, as well as variant frequencies from a diverse patient cohort.
Multiscale analysis of structurally conserved motifs
Authors: Cazals F. , Tetley R.
Published: July 2018

This work develops a generic framework to perform a multiscale structural analysis of two structures (homologous proteins, conformations) undergoing conformational changes. Practically, given a seed structural alignment, we identify structural motifs with a hierarchical structure, characterized by three unique properties. First, the hierarchical structure sheds light on the trade-off between size and flexibility. Second, motifs can be combined to perform an overall comparison of the input structures in terms of combined RMSD - an improvement over the classical least RMSD. Third, motifs can be used to seed iterative aligners, and to design hybrid sequence-structure profile HMM characterizing protein families.

From the methods standpoint, our framework is reminiscent from the bootstrap and combines concepts from rigidity analysis (distance difference matrices), graph theory, computational geometry (space filling diagrams), and topology (topological persistence).

On challenging cases (class II fusion proteins, flexible molecules) we illustrate the ability of our tools to localize conformational changes, shedding light of commonalities of structures which would otherwise appear as radically different.

Our tools are available within the Structural Bioinformatics Library (http://sbl.inria.fr). We anticipate that they will be of interest to perform structural comparisons at large, and for remote homology detection.
Adaptive introgression: an untapped evolutionary mechanism for crop adaptation
Authors: Burgarella Concetta , Barnaud Adeline , Ardo Kane Ndjido , Jankowsky Frédérique , Scarcelli Nora , Billot Claire , Vigouroux Yves , Berthouly-Salazar Cécile
Published: July 2018

Global environmental changes strongly impact wild and domesticated species biology and their associated ecosystem services. For crops, global warming has led to significant changes in terms of phenology and/or yield. To respond to the agricultural challenges of this century, there is a strong need for harnessing the genetic variability of crops and adapting them to new conditions. Gene flow, from either the same species or a different species, may be an immediate primary source to widen genetic diversity and adaptions to various environments. When the incorporation of a foreign variant leads to an increase of the fitness of the recipient pool, it is referred to as “adaptive introgression”. Crop species are excellent case studies of this phenomenon since their genetic variability has been considerably reduced over space and time but most of them continue exchanging genetic material with their wild relatives. In this paper, we review studies of adaptive introgression, presenting methodological approaches and challenges to detecting it. We pay particular attention to the potential of this evolutionary mechanism for the adaptation of crops. Furthermore, we discuss the importance of farmers’ knowledge and practices in shaping wild-to-crop gene flow. Finally, we argue that screening the wild introgression already existing in the cultivated gene pool may be an effective strategy for uncovering wild diversity relevant for crop adaptation to current environmental changes and for informing new breeding directions.
Activin signaling informs the graded pattern of terminal mitosis and hair cell differentiation in the mammalian cochlea
Authors: Prajapati-DiNubila Meenakshi , Benito-Gonzalez Ana , Golden Erin J. , Zhang Shuran , Doetzlhofer Angelika
Published: July 2018

The mammalian auditory sensory epithelium has one of the most stereotyped cellular patterns known in vertebrates. Mechano-sensory hair cells are arranged in precise rows, with one row of inner and three rows of outer hair cells spanning the length of the spiral-shaped sensory epithelium. Aiding such precise cellular patterning, differentiation of the auditory sensory epithelium is precisely timed and follows a steep longitudinal gradient. The molecular signals that promote auditory sensory differentiation and instruct its graded pattern are largely unknown. Here, we identify Activin A as an activator of hair cell differentiation and show, using mouse genetic approaches, that a local gradient of Activin A signaling within the auditory sensory epithelium times the longitudinal gradient of hair cell differentiation. Furthermore, we provide evidence that Activin-type signaling regulates a radial gradient of terminal mitosis within the auditory sensory epithelium, which constitutes a novel mechanism for limiting the number of inner hair cells being produced.
Decreased snow cover stimulates under ice primary producers, but impairs methanotrophic capacity
Authors: Garcia Sarahi L , Szekely Anna J. , Bergvall Christoffer , Schattenhofer Martha , Peura Sari
Published: July 2018

Climate change scenarios anticipate decrease of spring snow cover in boreal and subarctic regions. Forest lakes are abundant in these regions and substantial contributors of methane emissions. We performed an experiment on an anoxic frozen lake and observed that the removal of snow increased light penetration through the ice into the water modifying the microbial composition across depths. A shift in photosynthetic primary production was reflected by the increase of chlorophyll a and b concentrations in the upper depths of the water column, while Chlorobia, one of the key photosynthetic bacteria in anoxic lakes, shifted to lower depths. Moreover, a decrease in abundance of methanotrophs, such as Methylococcaceae, was noted concurrently to an increase in methane concentration in the water column. These results indicate that decrease of snow cover impacts both primary production and methane production/consumption, ultimately leading to increased methane emissions after spring ice off.
A bipartite transcription factor module controlling expression in the bundle sheath ofArabidopsis thaliana
Authors: Dickinson Patrick J. , Kneřová Jana , Szecówka Marek , Stevenson Sean S. , Burgess Steven J. , Mulvey Hugh , Bågman Anne-Maarit , Gaudinier Allison , Brady Siobhan M. , Hibberd Julian M.
Published: July 2018

C4photosynthesis evolved repeatedly from the ancestral C3state, improving photosynthetic efficiency by ∼50%. In most C4lineages photosynthesis is compartmented between mesophyll and bundle sheath cells but how gene expression is restricted to these cell types is poorly understood. Using the C3modelArabidopsis thalianawe identifiedcis-elements and transcription factors driving expression in bundle sheath strands. Upstream of the bundle sheath preferentially expressedMYB76gene we identified a region necessary and sufficient for expression containing twocis-elements associated with the MYC and MYB families of transcription factors.MYB76expression is reduced in mutant alleles for each. Moreover, down-regulated genes shared by both mutants are preferentially expressed in the bundle sheath. Our findings are broadly relevant for understanding the spatial patterning of gene expression, provide specific insights into mechanisms associated with evolution of C4photosynthesis and identify a short tuneable sequence for manipulating gene expression in the bundle sheath.
Phylodynamic analysis of the historical spread of Toscana virus around the Mediterranean
Authors: Cusi M. Grazia , Gandolfo Claudia , Savellini Gianni Gori , Terrosi Chiara , Sadler Rebecca A. , Gatherer Derek
Published: July 2018

All available sequences of the three genome segments of Toscana virus with date and location of sampling were analysed using Bayesian phylodynamic methods. We estimate that extant Toscana virus strains had a common ancestor in the late 16th to early 17th century AD, in territories controlled by the Ottoman Empire, giving rise to an ancestral genotype A/B in north Africa and to genotype C in the Balkans. Subsequent spread into western Europe may have occurred during the period of European colonization of north Africa in the 19th and early 20th centuries AD, establishing genotypes A and B in Italy and Spain respectively. Very little positive evolutionary selection pressure is detectable in Toscana virus, suggesting that the virus has become well adapted to its human hosts. There is also no convincing evidence of reassortment between genome segments, despite genotypes A and B now co-circulating in several countries.
Female vocalizations predict reproductive output in Brown-headed Cowbirds (Molothrus ater)
Authors: Kohn Gregory M.
Published: July 2018

Pair bonds are often maintained through the reciprocal and coordinated exchange of communicative signals. The ability to recognize and appropriately respond to a partner’s signals will define a pair’s ability to reproduce. Individual variation in responsiveness, by shaping the formation and maintenance of strong pair bonds, will ultimately influence an individual’s reproductive output. Throughout the breeding period, female cowbirds (Molothrus ater) respond to male song displays using a vocalization known as the chatter. In this study, we investigated whether variation in chatters remained repeatable across years and predicted reproductive performance. A flock of cowbirds housed in a large aviary complex was observed during the spring of 2011 to 2012. We recorded courtship interactions, including singing behavior for males, and chatters and eggs laid by females. The rate with which females responded to song using chatters remained consistent across years, with some females predictably responding to more songs using chatters than others. During 2012, chattering predicted the number of eggs females laid and her paired status. Paired females were more likely to respond to songs with chatters, and there was a strong positive relationship between the number of eggs laid and the proportion of songs she responded to using chatters. Overall, these findings suggest that individual variation in female vocal responsiveness is an important contributing factor to cowbird reproductive success.
Subsection corrosion inhibition of acidic-oxidized polymer degradant in offshore oil field
Authors: Zhu Yanhua , Zhao Liqiang , Liu Pingli , Yang Ming
Published: July 2018

Purpose

This paper aims to introduce a method to reduce corrosion caused by acidic-oxidized polymer degradant through subsection injection with different inhibitor.

Design/methodology/approach

This paper introduced a method to reduce corrosion caused by acidic-oxidized polymer degradant through subsection injection with different inhibitor.

Findings

The experimental results indicated that the influence of pre-corrosion status on corrosion rate and effectiveness of corrosion inhibitor are significant. The corrosion inhibitors in both injection stage inhibited the corrosion process by preventing the contact of corrosive medium and steel surface through formation of a protective film on the surface of N80 steel. The corrosion rate of polymer degradant can be reduced to 0.63 g/m 2 h through subsection injection with different inhibitor.

Originality/value

This result will increase the production of polymer injection plugging wells through expanding the application of acidic-oxidized polymer degradant.