bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of the vesicular GABA transporter within neuromedin S
+
neurons sustains behavioral circadian rhythms
Authors: Bussi Ivana L. , Neitz Alexandra F. , Sanchez Raymond E. A. , Casiraghi Leandro P. , Moldavan Michael , Kunda Divya , Allen Charles N. , Evans Jennifer A. , de la Iglesia Horacio O.
Published: November 2023

The suprachiasmatic nucleus (SCN) of the hypothalamus is the site of a central circadian clock that orchestrates overt rhythms of physiology and behavior. Circadian timekeeping requires intercellular communication among SCN neurons, and multiple signaling pathways contribute to SCN network coupling. Gamma-aminobutyric acid (GABA) is produced by virtually all SCN neurons, and previous work demonstrates that this transmitter regulates coupling in the adult SCN but is not essential for the nucleus to sustain overt circadian rhythms. Here, we show that the deletion of the gene that codes for the GABA vesicular transporter
Vgat
from neuromedin-S (NMS)
+
neurons—a subset of neurons critical for SCN function—causes arrhythmia of locomotor activity and sleep. Further, NMS-
Vgat
deletion impairs intrinsic clock gene rhythms in SCN explants cultured ex vivo. Although vasoactive intestinal polypeptide (VIP) is critical for SCN function,
Vgat
deletion from VIP-expressing neurons did not lead to circadian arrhythmia in locomotor activity rhythms. Likewise, adult SCN-specific deletion of
Vgat
led to mild impairment of behavioral rhythms. Our results suggest that while the removal of GABA release from the adult SCN does not affect the pacemaker’s ability to sustain overt circadian rhythms, its removal from a critical subset of neurons within the SCN throughout development removes the nucleus ability to sustain circadian rhythms. Our findings support a model in which SCN GABA release is critical for the developmental establishment of intercellular network properties that define the SCN as a central pacemaker.
Effect of the dipolar interaction on the dynamic hysteresis properties of 2D-nanodisks: out of plane driving field case
Authors: Çam Necda , Akıncı Ümit
Published: November 2023

We have systematically investigated the effect of dipolar interaction strength on the dynamical hysteresis behavior of the in-plane uniaxial anisotropic nanodisk system modeled by the classical Heisenberg model under the effect of the time-dependent external out-of-plane periodic magnetic field. Dynamical hysteresis loops, as well as hysteresis quantities (hysteresis loop area, coercive field, remanent magnetization), have been examined both in-plane and out-of-plane magnetization components by means of Monte Carlo simulation based on Metropolis Algorithm. Our simulation results suggest that the response of the in-plane and out-of-plane components of the magnetization have different hysteresis characteristics. For instance, while the out-of-plane component of the magnetization has ordinary dynamically disordered hysteresis curves, bowtie-shaped hysteresis loops have been obtained for the in-plane component of the magnetization. Disappeared dynamical order has been observed with the rising strength of the dipolar interaction.
Measurement of the voltage evolution on a load of X-pinch plasma system using the Pockels effect
Authors: Choi Seongmin , Ham Seunggi , Ryu Jonghyeon , Park Sungbin , Kim Jung-Hwa , Choi YeongHwan , Chung Kyoung-Jae , Hwang Y.S. , Ghim Y.-c.
Published: November 2023

A diagnostic system using the Pockels effect (linear electro-optic effect) has been developed to measure a voltage on a load of the SNU X-pinch device [Ryu et al., Rev. Sci. Instrum. 92, 053533 (2021)]. The sensor component of the diagnostic system comprises of a lithium niobate (LN) crystal and its mount. When the LN crystal is subjected to an external electric field, the refractive indices of the LN crystal change due to the Pockels effect, leading to a change in the polarization state of the propagating laser beam through the crystal. This concept allows the separation and shielding of electronic devices from the intense electric pulses generated by the X-pinch system. Furthermore, the compact size and high electric field tolerance of the LN crystal enable us to position the sensor in a close proximity to the load of the X-pinch, facilitating the measurement of voltage evolution on the load. In contrast to circuit-based voltage probes, our sensor possesses low inductance, allowing us to measure resistive-dominant voltage even in the presence of rapid current changes within the X-pinch system. In this paper, we outline the configuration of our voltage measurement system using the LN crystal within the X-pinch device and provide measurement results of the load voltage. Additionally, we explore the temporal evolution of the voltage in relation to the phase transition of the load.
Urban growth modeling for the assessment of future climate and disaster risks: approaches, gaps and needs
Authors: Reimuth Andrea , Hagenlocher Michael , Yang Liang Emlyn , Katzschner Antje , Harb Mostapha , Garschagen Matthias
Published: November 2023

Urban climate-related disaster risks are set to rise, driven by the interaction of two global megatrends: urbanization and climate change. A detailed understanding of whether, where and how cities are growing within or into hazard-prone areas is an urgent prerequisite for assessing future risk trajectories, risk-informed planning, and adaptation decisions. However, this analysis has been mostly neglected to date, as most climate change and disaster risk research has focused on the assessment of future hazard trends but less on the assessment of how socio-economic changes affect future hazard exposure. Urban growth and expansion modeling provide a powerful tool, given that urban growth is a major driver of future disaster risk in cities. The paper reviews the achievements lately made in urban growth and exposure modeling and assesses how they can be applied in the context of future-oriented urban risk assessment and the planning of adaptation measures. It also analyses which methodological challenges persist in urban growth and exposure modeling and how they might be overcome. These points pertain particularly to the need to consider and integrate (1) urban morphology patterns and potential linkages to exposure as well as vulnerability, (2) long-term time horizons to consider long-term developments, (3) feedbacks between urbanization trajectories and hazard trends, (4) the integration of future urban growth drivers and adaptation responses, (5) feedbacks between adaptation and urbanization, and (6) scenarios, which are developed within a commonly defined scenario framework.
What drives historical and future changes in photovoltaic power production from the perspective of global warming?
Authors: Constantin Scheele Robert , Fiedler Stephanie
Published: November 2023

We investigate the drivers of global and regional changes in the potential for photovoltaic (PV) power production from the pre-industrial (1850) to present-day (1985–2014) and until the end of the century (2071–2100), based on output from the Coupled Model Intercomparison Project phase six (CMIP6). Our assessment separates regional contributions from changes in clouds, humidity, temperature, aerosols, and wind speed to the changes in PV power potentials for the first time. Present-day PV power potentials are adversely affected by anthropogenic aerosols compared to the pre-industrial, with a global decrease of the PV power potential by −1.3%. Our results highlight a globally averaged decrease in future PV power potentials primarily driven by temperature and humidity increases by −1.2% to more than −3.5%, depending on the scenario. Regionally different contributions of changes in clouds and aerosols cause heterogeneous spatial patterns in changes of PV potentials, with typically stronger (weaker) influences from clouds (aerosols) in SSP5-8.5 compared to SSP1-2.6. Our results imply that the uncertain response of clouds to warming and aerosol effects are hurdles in quantifying changes in the regional potentials for PV power production.
Paramagnetic two-dimensional silicon-oxide from natural silicates
Authors: Mahapatra Preeti Lata , de Oliveira Caique Campos , Costin Gelu , Sarkar Suman , Autreto Pedro A S , Tiwary Chandra Sekhar
Published: November 2023

Silicon dioxide’s potential for having magnetic properties is fascinating, as combining its electronic capabilities with magnetic response seems promising for spintronics. In this work, the mechanisms that drive the change from diamagnetic behavior in pure silicates like SiO2 to paramagnetic behavior in transition metal-doped silicates like Rhodonite silicate (CaMn3Mn(Si5O15)) are explored. This naturally occurring Rhodonite (R)-silicate was thinned down while retaining its magnetic properties by liquid-phase scalable exfoliation. Exfoliating R-silicate into the two-dimensional (2D) structure by LPE increases magnetic coercivity, and the internal resistance to demagnetization (ΔHc) up to ∼23.95 Oe compared to 7.08 Oe for its bulk phase. DFT spin-polarized calculations corroborate those findings and explain that the origin of the magnetic moment comes mainly from the Mn in the doped 2D silicate due to the asymmetrical components of the Mn d and Si p states in the valence band. This result is further illustrated by the spin component differential charge densities showing that Mn and Si atoms display a residual up spin charge. Rhodonite’s unusual magnetic behavior has considerable potential for spintronics, data storage, and sensing technologies. Understanding the complex relationships between the structural, magnetic, and electronic properties of silicates is essential for developing new materials and composites as well as for driving future research.
MXene Fe2C as a promising candidate for the 2D XY ferromagnet
Authors: Agapov E M , Kruglov I A , Katanin A A
Published: November 2023

Monolayer Fe2C is expected to possess strong electronic correlations, which can significantly contribute to electronic and magnetic properties. In this study we consider electronic and magnetic properties of MXene Fe2C within the DFT+DMFT approach. We establish the existence of local magnetic moments

μ

l
o
c

=
3.3

μ
B

in this compound, characterized by sufficiently long lifetime of

τ
∼
350

 fs. We also calculate exchange interaction parameters accounting for electronic correlations using the recently developed approach for paramagnetic phase. At low temperatures, we obtain the strongest exchange interaction 11 meV between next nearest neighboring Fe atoms, located above (or below) the carbon plane, and the subleading interaction 6 meV between the next to next nearest neighboring atoms, located across the carbon plane. The resulting dependence of the Berzinskii–Kosterlitz–Thouless (BKT) and Curie temperatures on magnetic anisotropy is obtained. The BKT temperature for the pristine Fe2C is

T

B
K
T

≃
300

 K, which makes this compound a good candidate for the two-dimensional ferromagnet with XY anisotropy.
Performance assessment of surface modified natural fibre using NaOH in composite concrete
Authors: Priya C , Sudalaimani K
Published: November 2023

Abaca fiber degradation in concrete owing to its alkaline nature decreases the strength of concrete. This research focuses on overcoming the degradation by alkaline treatment with sodium hydroxide (NaOH) to improve fiber performance. This study was completed with the extraction process of fiber, mechanical properties, micro-structural analysis of composite fiber concrete for both M30 and M40 grades, and durability performance if the fiber content, aspect ratio of fiber and molarities of Sodium Hydroxide were optimized using splitting tensile strength of the concrete matrix and it was found that the optimum percentage of fiber content was 1% at 12% alkali treatment. The composite concrete has achieved an increase of 2700 to 3100 kg m−2 in split tensile strength with treated abaca fibers compared to untreated fiber concrete. In addition, treated abaca fiber concrete provides better performance in mechanical and durability studies. The binding nature of fiber concrete is better than that of conventional concrete, which is evidenced in microstructural analysis. This study ultimately concluded that the treated abaca fiber composite concrete is a better alternative to commercially available untreated abaca fibers and other natural fibers.
Generic and mod 𝑝 Kazhdan-Lusztig Theory for 𝐺𝐿₂
Authors: Pepin Cédric , Schmidt Tobias
Published: November 2023

Let

F
F

be a non-archimedean local field with residue field

F

q

\mathbb {F}_q

and let

G

=
G

L

2

/

F

\mathbf {G}=GL_{2/F}

. Let

q

\mathbf {q}

be an indeterminate and let

H

(
1
)

(

q

)

\mathcal {H}^{(1)}(\mathbf {q})

be the generic pro-

p
p

Iwahori-Hecke algebra of the

p
p

-adic group

G

(
F
)

\mathbf {G}(F)

. Let

V

G
^

V_{\mathbf {\widehat {G}}}

be the Vinberg monoid of the dual group

G
^

\mathbf {\widehat {G}}

. We establish a generic version for

H

(
1
)

(

q

)

\mathcal {H}^{(1)}(\mathbf {q})

of the Kazhdan-Lusztig-Ginzburg spherical representation, the Bernstein map and the Satake isomorphism. We define the flag variety for the monoid

V

G
^

V_{\mathbf {\widehat {G}}}

and establish the characteristic map in its equivariant

K
K

-theory. These generic constructions recover the classical ones after the specialization

q

=
q
∈

C

\mathbf {q}=q\in \mathbb {C}

. At

q

=
q
=
0
∈

F

¯

q

\mathbf {q}=q=0\in \overline {\mathbb {F}}_q

, the spherical map provides a dual parametrization of all the irreducible

H

F

¯

q

(
1
)

(
0
)

\mathcal {H}^{(1)}_{\overline {\mathbb {F}}_q}(0)

-modules.
Accessibility of SPDEs driven by pure jump noise and its applications
Authors: Wang Jian , Yang Hao , Zhai Jianliang , Zhang Tusheng
Published: November 2023

In this paper, we develop a new method to obtain the accessibility of stochastic partial differential equations driven by additive pure jump noise. An important novelty of this paper is to allow the driving noises to be degenerate. As an application, for the first time, we obtain the accessibility of a class of stochastic equations driven by pure jump (possibly degenerate) noise, including stochastic 2D Navier-Stokes equations, stochastic Burgers equations, stochastic singular

p
p

-Laplace equations, and stochastic fast diffusion equations. As a further application, we establish the ergodicity of stochastic singular

p
p

-Laplace equations and stochastic fast diffusion equations driven by additive pure jump noise, and we remark that the driving noises could be Compound Poisson processes or Lévy processes with heavy tails.
A Rare Autopsy Case of Aggressive Combined Hepatocellular-Cholangiocarcinoma with Stem Cell Features in A 59-Year-Old Female
Authors: Ahmed A A , Gehris B T , McDonald M , Salihi S Al , Buja M
Published: November 2023

Introduction/Objective

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare liver tumor with histologic and phenotypic features of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. It is believed to arise from hepatic progenitor cells. It consists of intermingled malignant biliary and hepatic tissue and thus is a distinct entity, rather than two separate coexisting malignancies.

Methods/Case Report

A 59-year-old female with a history of hepatitis C and cirrhosis presented with abdominal pain, shortness of breath, and altered mental status. She developed hematemesis and went into cardiac arrest. Massive transfusion and cardiopulmonary resuscitation were initiated. She was intubated, and an esophageal/gastric balloon was placed. She then underwent a procedure to relieve portal hypertension and related gastrointestinal bleeding.

Despite extensive interventions, her condition continued to deteriorate. She expired one day after her initial presentation.

Results (if a Case Study enter NA)

At autopsy, the liver was diffusely and markedly fibrotic with numerous nodules of varying size with invasion into adjacent vasculature. Microscopic examination of the nodules revealed cHCC-CC with stem cell features and lymphovascular invasion. Further examination revealed tumor emboli scattered throughout the right lung.

The patient’s history of chronic hepatitis C may have contributed to the development of her cHCC-CC. Although gross appearance resembled cirrhosis, upon microscopic inspection the nodules showed excessive tumor burden.

Ultimately the patient had end stage liver disease due to the accumulation of damage and consequent fibrosis. This led to portal hypertension with subsequent massive gastrointestinal bleeding, hemorrhagic shock, and death.

Conclusion

cHCC-CC is a rare aggressive primary liver tumor with a poor prognosis. It can present with a cirrhotomemetic pattern with small nodules that can evade clinical and radiographic detection. Autopsy findings can provide valuable insights into the pathogenesis and clinical course of cHCC-CC, highlight the aggressive nature of the disease, and may inform future diagnostic and therapeutic strategies. Accurate diagnosis of this tumor is important for patient management and prognostication.
The Informative & Virtuous Role of Autopsy Observation Experiences in Medical Student Education
Authors: Hagen E S , Quintanilla-Arteaga A , Lilley C M , Mirza K M
Published: November 2023

Introduction/Objective

The autopsy is an extremely valuable resource to medicine and society. However, there has been a significant decline in autopsy rates. The autopsy is a currently overlooked part of medical education. We conducted a study to understand medical students’ experiences with observing an autopsy. We assessed the impact of autopsy observation on medical students’ consideration of Pathology as a specialty choice. We also explored the possible emotional burden of observing an autopsy.

Methods/Case Report

The Pathology Interest Group at the Stritch School of Medicine (SCOPE) collaborated with the LUMC Pathology department to offer medical students the opportunity to observe an autopsy performed at the university. Participants completed surveys before and after their autopsy observation experiences through Google forms. Data collected over one academic year was analyzed using descriptive statistics and independent sample T- tests where applicable. The participants’ responses to open-ended questions were reviewed and coded by ESH and ASQ.

Results (if a Case Study enter NA)

Nineteen students participated in the study. One participant’s data was excluded given conflict of interest; thus, 18 students’ data were analyzed. Eight students (44.4%) were M1’s, six (33.3%) were M2’s, and four (22.2%) were M3’s. None (0%) of the students previously observed an autopsy. Unifying themes emerged regarding students’ thoughts about the autopsy observation opportunity, including excitement, gratitude, nervousness, humility, learning opportunity/curiosity, and heart-wrenching. Ten (55.6%) students expressed at least some level of concern about the emotional burden of the autopsy, which four students (22.2%) endorsed feeling afterward. Likert scores revealed that none (0%) of the students felt uncomfortable describing the process of an autopsy to a decedent’s family after autopsy observation and 13 students (72.2%) felt highly comfortable.

Conclusion

The participants widely found autopsy observation to be highly valuable, regardless of their consideration of Pathology as a career. Although the autopsy observation experiences did not lead more students to consider Pathology, the autopsy is just one of the many aspects of Pathology and we encourage ongoing communication of this idea to trainees. The sentiments expressed by students could inform design of informative and virtuous autopsy observation opportunities. Limitations of the study included its limited generalizability and small sample size, yet data collection is ongoing.
A rare case of cardiac calcified amorphous tumor in a 34-year-old woman diagnosed at autopsy
Authors: Odujoko O , Asad M , Bal S K , Dodge J , Janjua J
Published: November 2023

Introduction/Objective

Cardiac calcified amorphous tumor (CAT) is an uncommon, non-neoplastic heart lesion with an unknown incidence due to its rarity. Some authors have reported a female predominance of 62.5%. Many cases are associated with end-stage renal disease, diabetes mellitus and coronary artery disease. Dysfunction of calcium- phosphorus metabolism and hypercoagulability are thought to contribute to its pathogenesis. This is the first case reported from our institution.

Methods/Case Report

We present the case of a 34-year-old woman with a remote history of ulcerative colitis, type 1 diabetes mellitus, hypertension, Hashimoto thyroiditis, cardiomegaly, and end-stage renal disease on continuous hemodialysis. She had multiple hospitalizations for mesenteric ischemia and small bowel resections. She was admitted multiple times in 2021 for complaints of pain in bilateral thighs, shortness of breath, frequent loose stools, and abdominal pain. She was poorly compliant with hemodialysis. A chest x-ray showed severe enlargement of the cardiac silhouette. A CT angiogram of the abdomen and pelvis showed arteriosclerosis of the superior mesenteric, inferior mesenteric and celiac arteries. The patient presented to the hospital in February 2022 with continuous abdominal pain, gluteal pain, and diarrhea. Her creatinine was consistently elevated at 3.52 mg/dL. On the sixth day of admission, she was found unresponsive and was pronounced dead. Autopsy showed cardiomegaly (600 grams) with left ventricular hypertrophy, recent myocardial infarction of the posterolateral left ventricle and moderate to severe coronary artery atherosclerosis. There were lesions composed of calcified amorphous material involving the mitral valve, the endocardium and subendocardial portions of the left and right ventricles, consistent with multifocal cardiac calcified amorphous tumor. The largest lesion measured 4.0 cm. The cause of death was myocardial infarction complicating type 1 diabetes mellitus and end-stage renal disease.

Results (if a Case Study enter NA)

NA

Conclusion

CATs are usually asymptomatic but possible symptoms include dyspnea and syncope. As a result, they are often incidental findings. The calcified deposits may embolize, causing pulmonary embolism and cerebral infarction. CAT is most frequently observed in the left heart, especially on the mitral annulus; however, the right side of the heart can also be affected. End-stage renal disease is a predisposing condition, as seen in this patient.
ACTB::GLI1 Gene Fusion Small Bowel Mesenteric Tumor; a Case Report and Review of the Literature
Authors: Abdelsadek O A , Mehreen A , Alnajar H
Published: November 2023

Introduction/Objective

GLI1 encodes a transcription factor that targets cell cycle regulators affecting stem cell proliferation. Activation of the GLI (glioma-associated oncogene homologue 1). GLI activity in adult tissues is restricted but has been identified in various neoplasms, as a result of mutations in the PTCH (patched) or SMOH (smoothened) genes, encoding components of the sonic hedgehog pathway, or by amplification of GLI. The B-actin (ACTB) gene, encoding an essential cytoskeletal component, is under the control of a conserved, strong, and complex promoter that assures a high level of expression in non-muscle cells. ACTB::GLI1 gene fusions have been reported in the tongue as the pathognomonic genetic abnormality defining an unusual subset of actin-positive, perivascular tumors with t (7;12) translocation.

Methods/Case Report

We report a case of 53-year-old male presented to the hospital with dizziness and bloody stools. CT scan of the abdomen and pelvis revealed a 10.5 x 7.7 cm large complex cystic and solid mass of the right lower quadrant of the abdomen adjacent to the cecum and terminal ileum. The patient has a past medical history of testicular germ cell tumor and underwent orchiectomy with adjuvant chemotherapy 30 years ago. The mass was excised and histological examination of the mass showed an unencapsulated, relatively circumscribed neoplasm composed of sheets of monomorphic bland spindle to ovoid cells. Immunohistochemical (IHC) stains, including pan- CK, SALL4, c-Kit, CD34, SMA, MDM2, HMB45, and MART1, were all negative. NGS sarcoma fusion panel was done and revealed ACTB::GLI1 gene fusion. The tumor was finally diagnosed as GLI1 -rearranged enteric tumor.

Results (if a Case Study enter NA)

NA

Conclusion

our case, in addition to, previously reported cases in the literature support the existence of a newly identified, seemingly discrete group of soft tissue tumors at different body locations. The morphology of these tumors is somewhat variable, making identifying and diagnosing these tumors more challenging. In addition to the morphologic variance, the diagnosis of these tumors in unusual locations is not uncommon, with some variations in IHC staining patterns. Identifying the molecular pattern of these tumors and the biological mechanism will facilitate more effective treatment options for patients, including targeted therapy.
Myxofibrosarcoma with false-positive EWSR1 FISH
Authors: Lack M , Cain S , Hamza A , Meyer A R
Published: November 2023

Introduction/Objective

Myxofibrosarcoma is a common sarcoma in elderly patients. It comprises a spectrum of malignant fibroblastic neoplasms with variable myxoid stroma, pleomorphism, and a distinctive curvilinear vascular pattern. As soft tissue tumors frequently exhibit overlapping histologic features, immunohistochemical stains and fluorescent in situ hybridization (FISH) studies are utilized to determine accurate diagnosis. The purpose of this case is to report a false-positive EWSR1 FISH in a myxofibrosarcoma.

Methods/Case Report

A 54-year-old male presented with a mass in his left forearm that had been present for four months. The mass was as painless and had not grown larger since it was initially noticed. A resection of the mass was performed which revealed monotonous, spindled to focally epithelioid cell population in a myxoid background that bordered on chondroid in some foci. While this raised concern for a translocation-associated sarcoma, particularly extraskeletal myxoid chondrosarcoma, the scattered pleomorphism expected in a myxofibrosarcoma was still present. Immunohistochemistry revealed diffuse reactivity for CD34 and negativity for pancytokeratin, EMA, S100, SOX10, desmin, SMA, CD117, TLE1, and STAT6 stains. FISH for EWSR1 gene arrangement to exclude extraskeletal myxoid chondrosarcoma was positive. However, a follow-up NGS study was negative for gene rearrangement, indicating a false-positive FISH result. The diagnosis of myxofibrosarcoma, FNCLCC grade 1 or 3 was rendered.

Results (if a Case Study enter NA)

NA

Conclusion

EWSR1 gene rearrangements represent one of the most commonly involved genes in sarcoma. FISH has a reported sensitivity and specificity for this rearrangement of 100% and 87% respectively. This case highlights a false-positive FISH result in a soft tissue tumor and the importance of correlating results with histology and molecular genetics for accurate diagnosis to guide appropriate management for patients.
Tissue microarray immnunohistochemical staining for androgen receptor in breast cancer in a Ghanaian cohort
Authors: Duduyemi B M , Ayibor W , Agyemang-Yeboah F
Published: November 2023

Introduction/Objective

Despite the advancement in therapy, breast cancer still remains the commonest malignancy in women globally due in part to its heterogeneity. Triple negative breast cancer (TNBC) represents up to 20% of all breast cancer variants, an aggressive disease with poorer outcomes compared to other breast cancer subtypes. No targeted therapies are currently approved for TNBC, and newer treatment approaches are seriously needed.

Androgen receptor (AR), another hormonal receptor, is often expressed in breast cancer and its role depends on the relative levels of circulating estrogens and androgens. This study aims to assess the expression of AR in breast cancer in a tertiary hospital in Ghana

Methods/Case Report

Immunohistochemical staining for AR was performed on tissue microarray (TMA) blocks of which ER, PR, Her-2/neu had already been done. 197 cases were suitable for the study. Results from the immunostaining were analysed using SPSS version 23 for descriptive statistics and correlations (X2 and Pearson tests)

Results (if a Case Study enter NA)

197 TMA cases were used. TNBCs constitute 61.9% of the cancers. The majority of these tumours were grade III, ductal carcinoma NST. The mean age was 49.86±14.09 and the modal age group was the 40-49 years. Our cases showed 23% AR expression in triple negative cancers. The study also established that AR is more frequently expressed in low grade tumours compared to the high-grade ones.

Conclusion

There is appreciable level of AR expression in our cases but most are quadruple negative. However, AR is more frequently expressed in low grade tumours than high grade ones
The correlation between Plasma Fibrinogen Levels and Glycemic Status in type 2 Diabetes Mellitus
Authors: Abdelmonem M , Abdulla S , Wasim H , Elawamy H
Published: November 2023

Introduction/Objective

Background: Fibrinogen is considered a well-known contributor to the progression of atherosclerotic lesions and a predictor of cardiovascular events. Patients with diabetes mellitus (DM) have higher levels of fibrinogen, which may raise their thromboembolic risk for cardiovascular disease (CVD). Plasma fibrinogen is an indicator of inflammation, and endothelial dysfunction has been described as an independent risk factor for cardiovascular morbidity in type-2 diabetes mellitus (T2DM) patients. Poor glycemic control has been reported to be associated with hyperfibrinogenemia.

Aim

This study aims to estimate the levels of fibrinogen in patients with type-2 diabetes mellitus and determine its correlation with glycated hemoglobin levels.

Methods/Case Report

Subjects and methods: It is a cross-sectional analytic study conducted in the Benghazi Diabetic Clinic, Libya. Patients who were diagnosed with type 2 diabetes mellitus, either newly detected or already on diet or treatments, were included in the study during the period between May 2022 to December 2022. A total of 231 adult subjects were selected, with ages ranging from 20-80 years. Random blood sugar levels were assessed. Plasma fibrinogen levels (mg/dl) were estimated by the "Clauss method" and glycosylated hemoglobin (%) by the "immunoturbidimetric method." Patients were categorized into three groups depending upon the HbA1c values, i.e., into <5.7% (good control), 5.7-6.5% (fair control), and >6.5% (poor control).

Results (if a Case Study enter NA)

Result: Out of 231 subjects, (40.6%) were males and (59.4%) were females, with a mean±SD of age was (47.03±15.54) years. There was a significant positive correlation between fibrinogen and HbA1c in the fair control group (r=0.424, p=0.003) and the poor control group (r=0.369, P=0.000). Moreover, the difference between fibrinogen and age in the good control group was significant (p>0.05), whereas no significance was recognized in other groups.

Conclusions

Plasma fibrinogen levels are elevated in type 2 DM, and this elevation was associated with poor glycemic control; increased HbA1c levels. The other parameters which correlated with plasma fibrinogen levels were age. Lowering plasma fibrinogen levels could be an integral approach to cardiovascular complications reduction in type-2 DM.
Accuracy of prior cytology versus intraoperative consultation in predicting the final diagnosis of thyroid specimens
Authors: Zhao J , Ding L , Fung P , Mathews E , Sullivan P
Published: November 2023

Introduction/Objective

The aim of this study was to assess the accuracy of preoperative cytology and the additional contribution of intraoperative frozen section in predicting the final diagnosis of thyroid surgical specimens.

Methods/Case Report

A retrospective search was conducted for cases that underwent pre-surgical cytology of thyroid surgical specimens received from January 2017 to June 2022. A total of 99 cases were evaluated which were grouped into six categories according to the Bethesda system. The cytology results were compared with the corresponding frozen section and permanent section diagnoses. Indeterminate and discordant cases were further evaluated with molecular tests.

Results (if a Case Study enter NA)

Among the 99 cases, preoperative cytologic diagnoses were as follows: 1 was nondiagnostic, 9 were benign, 7 were AUS/FLUS, 3 were FN/SFN, 7 were suspicious for malignancy, and 72 were malignant. Using Bethesda categories V and VI as cytology “positive” cases and Bethesda category II as cytology “negative” cases, the sensitivity and specificity of cytology were 99% and 100%, respectively. The positive predictive value was 100%. The negative predictive value was 89%, which was affected by sampling error. Intraoperative frozen section was performed on 31 cases. In 4 indeterminate cytology cases (Bethesda III, IV), frozen section diagnosis was benign in 1 (confirmed on final) and remained indeterminate in 3 cases (3 benign on final). All 3 dual indeterminate cases showed a follicular pattern; molecular tests were predictive of the final diagnosis in these cases. All 21 malignant frozen section diagnoses had positive cytology.

Conclusion

Cytology has high sensitivity and specificity, making it a valuable preoperative tool in thyroid surgery. Practically, intraoperative frozen section has limited value in thyroid nodules classified as Bethesda categories V and

VI. Additional evaluation may be helpful for cases classified as uncertain Bethesda categories. For follicular patterned lesions, frozen section may have less value.
Fine needle aspiration cytology of metastatic tumors to the thyroid: a 20-years single institution retrospective study
Authors: Saeed O A , Segura S , Hou T , Saad M , Alkhaseen A
Published: November 2023

Introduction/Objective

Metastases to the thyroid are rare and represent approximately 2% to 3% of all thyroid malignancies. In this study we aim to report our institution experience with these tumors over the last twenty years.

Methods/Case Report

Our laboratory information system was searched for metastatic tumors to the thyroid diagnosed on fine needle aspiration cytology from 2003 to 2023. The pathology reports as well as clinical data for these cases were then reviewed retrospectively.

Results (if a Case Study enter NA)

A total of 35 cases were found over the period of twenty years. The ages ranged from 30 to 83 with a mean of 60 years. 19 patients were female (54%) while 16 were males (46%). Clear cell renal cell carcinoma was the most common source of metastasis (12 cases), followed by squamous cell carcinoma of the head and neck (6 cases), followed by lung or breast adenocarcinoma, and neuroendocrine tumors (3 each). There were four metastatic sarcomas to the thyroid: osteosarcoma, synovial sarcoma, angiosarcoma and leiomyosarcoma. There was two metastatic adenocarcinoma (unknown primary), one melanoma case as well as one case of colon cancer.

Conclusion

Although rare, metastasis to the thyroid gland do happen and could be a potential diagnostic pitfall in a limited cytology specimen.
Atypical Facial Chondroid Syringoma of Medial Canthus, A rare clinical entity
Authors: Salehiazar S , Mirzaei Baboli K , Lores Gonzalez M , Ji P , Peng S
Published: November 2023

Introduction/Objective

Chondroid syringoma (CS) is an uncommon, benign mixed tumor originating from the sweat gland. Its incidence rate is extremely low, estimated to be less than 0.01%. CS predominantly affects adult males and shows a preference for the head and neck region. Typically, the size of the lesion is smaller than 1.0 cm, and it presents as a solitary, painless, subcutaneous nodule that is soft to firm, non-ulcerative, and gradually progressive.

Histologically, CS is characterized by a neoplasm composed of epithelial and myoepithelial cells, which are surrounded by a myxomatous, pseudochondromatous, or hyaline stroma containing mucous secretions. Although atypia is rare in CS, there is a potential for it to undergo malignant transformation.

Methods/Case Report

A 49-year-old man presented with a slowly growing mass on the medial canthus that had been present for 6 months. Examination revealed a tender, mobile nodule measuring 1.1 cm. An MRI of the head confirmed a subcutaneous lesion without involvement of deeper structures. Excisional biopsy of the lesion suggested adnexal carcinoma with involvement of the margins. The patient underwent Mohs surgery.Histopathology revealed localized basaloid epithelial proliferation forming solid sheets, trabecular, ductal structures with, chondroid myxoid stroma.

Immunohistochemically, the tumor cells of solid sheets and trabeculae were positive for CK5/6, P63, and Vimentin, whereas the cells were focally positive for S100, Calponin, alpha Actin, and SOX10. Also, ductal epithelial cells were highlighted with CK7, Cam5.2, EMA, and CEA. Ki-67 showed 1–5% reactivity. A few satellite nodules with infiltrative margins were seen. The atypical features, including cell atypia and a focal infiltrating border, suggest atypical chondroid syringoma. This tumor is considered a low-grade lesion, and no unequivocal evidence of malignancy has been identified.

Results (if a Case Study enter NA)

NA

Conclusion

Awareness of chondroid syringoma as a rare cause of eyelid lesions is important because although it is a benign neoplasm, incomplete excision can lead to recurrence or malignant transformation. Chondroid syringoma rarely exhibits atypia but can convert to the malignant spectrum. When malignant, it has a significant potential for recurrence, metastasis, and even death. Due to the tumor's rarity, making an accurate preoperative diagnosis can be challenging. Therefore, the possibility of chondroid syringoma should be kept in mind when dealing with a gradually progressive, soft to firm subcutaneous swelling.
Steroidogenic acute regulatory (StAR) protein is a useful marker for sex-cord-stroma tumors and normal/neoplastic adrenocortical tissue
Authors: Lennartz M , Amirzada D , Blessin N C , Gorbokon N , Hube-Magg C , Sauter G , Simon R , Kluth M , Bernreuther C , Steurer S , Krech T
Published: November 2023

Introduction/Objective

Steroidogenic acute regulatory (StAR) protein is a mitochondrial transport protein with a critical regulatory role for steroid hormone production. As its expression is limited to few normal tissues, the immunohistochemical analysis of StAR was proposed to be diagnostically useful.

Methods/Case Report

To comprehensively evaluate the diagnostic utility of immunohistochemical StAR expression analysis, a tissue microarray containing 19,202 samples from 152 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). Melan-A “cross-reactive” data were available from a previous study for comparison.

Results (if a Case Study enter NA)

StAR immunostaining occurred in 198 (1.2%) of the 17,135 analyzable tumors. StAR expression was observed in 27 of 152 tumor categories, 9 of which included at least one strongly positive case. The highest rate of StAR positivity occurred in Leydig cell tumors of the testis and the ovary (100%), steroid cell tumors of the ovary (100%), adrenocortical carcinomas (93%) and adenomas (87%), Sertoli-Leydig cell tumors (67%) and granulosa cell tumors of the ovary (56%) as well as in seminomas (7%). As compared to Melan A, StAR was more often positive in adrenocortical neoplasms and in Leydig cell tumors while StAR (but not Melan-A) was negative in Sertoli cell tumors.

Conclusion

Our data provide a complete overview on the patterns of StAR immunostaining in human tumors and suggest a diagnostic utility of StAR immunohistochemistry for supporting a diagnosis of Leydig cell tumors or of normal or neoplastic adrenocortical tissue. In contrast to Melan A, StAR appears to be more sensitive for these tumors while StAR is always negative in malignant melanoma, a frequent source of adrenal metastasis.
PD-L1 Expression Spatial Heterogeneity in Colorectal Adenocarcinoma
Authors: Jaramillo C , Hwang J , Brady R , Clifton G
Published: November 2023

Introduction/Objective

PD-L1 expression on colon cancer cells is associated with a worse prognosis[CGTLUMB(1] and may be an important selection marker in colon cancer patients for developing or combination immunotherapies in the future. A patient is eligible for targeted therapy if they demonstrate PD-L1 expression on a representative section, with different positivity threshold percentages used in different indications. However, little is known about the spatial heterogeneity of PD-L1 expression within tumors or how sampling bias may impact patient care. Here we report the results of a single institution retrospective study of PD-L1 heterogeneity in colorectal cancer to test the hypothesis that PD-L1 staining is homogenous throughout the tumor microenvironment.

Methods/Case Report

Long-term tissue storage at a single tertiary care center was queried for all cases of resectable (stage I-IV) colonic adenocarcinoma between 1 Jan 2014 and 1 Oct 2020. Cases with at least 4 formalin- fixed paraffin embedded blocks with tumor were selected; exclusion criteria included neoadjuvant therapy and absence of residual tumor on resection. 8 patients were identified meeting inclusion criteria (mean age 68 17 years,

5:3 M:F). PD-L1 (5H1 monoclonal antibody) immunohistochemistry was performed on corresponding tissue. Percent tumor cells expressing PD-L1 in a representative 1mm2 area at invasive margin and central tumor was quantified for

each section on digital slide images acquired on an Aperio CS2 Digital Slide Scanner (Leica Biosystems, Wetzlar, Germany) using QuPath (Version: 0.4.3).

Results (if a Case Study enter NA)

The mean ± SD of PD-L1 staining was 2.7±4.4% at invasive margin and 0.2±0.25% within central tumor; no statistically significant difference between regions was identified (paired t-test, p=0.15). Notably, 2 of the 8 cases demonstrated ranges at the invasive margin (0-36% and 1.3-35%) that span the cutoff for several commercially available anti-PD-1/PD-L1 agents.

Conclusion

These findings demonstrate that PD-L1 quantification can vary significantly within the same tumor depending on where counts are performed. This has significant clinical implications as PD-L1 positivity and patient eligibility for targeted therapy is most often assessed in a single location. Our current clinical methods of assessing PD-L1 expression do not account for the spatial complexities of the tumor microenvironment and could contribute to inaccuracy of small volume biopsies.
Beta-Catenin Nuclear Expression in Squamoid Morules in Colorectal Adenomas: Clinicopathologic Study of Fifteen Cases
Authors: Centeno B , Ghayouri M , Jiang K , Lauwers G , Nakanishi Y , Perez D , Wu T , Bhalla R
Published: November 2023

Introduction/Objective

Squamoid morules are an intriguing finding rarely seen in colorectal adenomas, mimicking foci of microinvasion or neuroendocrine differentiation. Previous observations include mostly case reports and small series, with few examining the squamoid morules in detail.

Methods/Case Report

We identified fifteen colorectal adenomas with squamoid morules and collected clinicopathological data including age, sex, procedure, location, pathologic diagnosis, and size. A representative block was chosen for immunohistochemistry in each case. The expression of p40, p63, CK5/6, beta-catenin, synaptophysin, chromogranin, and Ki-67 in squamoid morules were examined immunohistochemically.

Results (if a Case Study enter NA)

The fifteen patients comprised thirteen males and two females ranging in age from 45 to 85 years (average: 60.6 years old). The adenomas were removed by endoscopic resection (n = 7) or surgical resection (n = 8). Nine adenomas were found in the rectosigmoid colon, one in the descending colon, and five in the right colon. Eleven adenomas were tubulovillous adenomas (average: 3.8 cm, ranging 1.0 to 6.0 cm) and four were tubular adenomas (average: 2.6 cm, ranging 1.6 to 3.0 cm). Seven adenomas contained invasive adenocarcinoma. Squamoid morules were randomly distributed in adenomas. All foci of squamoid morules showed beta-catenin nuclear positivity and most (more than 90 %) showed CK5/6 expression. Squamoid morules were focally positive for p63 in three adenomas and focally positive for p40 in one adenoma. In one adenoma squamoid morules are positive for both synaptophysin and chromogranin. In all fifteen adenomas squamoid morules were negative for Ki- 67.

Conclusion

Squamoid morules are characterized by strong male predominance, association with large adenoma size, beta-catenin nuclear positivity, CK5/6 expression, and no Ki-67 expression. Beta-catenin nuclear expression is helpful in distinguishing squamoid morules from foci of microinvasion.
Challenges in Diagnosis of Steatohepatitic Hepatocellular Carcinoma on a Biopsy Specimen
Authors: Amin S E , Elzamly S , Ibrahim N , Zhang H
Published: November 2023

Introduction/Objective

Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Steatohepatitic hepatocellular carcinoma (SH-HCC) is a subtype that is associated with metabolic syndrome and alcoholic hepatitis. Diagnosing SH-HCC can be extremely challenging on a biopsy specimen, given that steatohepatitis-like changes can be seen in focal nodular hyperplasia and hepatic adenoma. Herein, we present a very challenging case of SH-HCC that was initially diagnosed as a well-differentiated lesion after multi-institutional consultations.

Methods/Case Report

A 54-year-old female with past medical history of diabetes and hypertension presented with flank pain and a 2.7 cm liver mass in a background of diffuse hepatic steatosis by CT scan, concerning for malignancy. Viral hepatitis serology workup was negative.

Results (if a Case Study enter NA)

The liver core biopsy reveals a well-differentiated hepatic lesion with areas of steatosis, fibrosis, and features of steatohepatitic changes including ballooning hepatocytes and Mallory-Denk bodies. No significant cytological atypia is identified. No definitive loss of reticulin is seen by reticulin stain. The cytological or architectural atypia was insufficient in isolation to diagnose HCC. The lesion cells are positive for HepPar-1 and Arginase-1, while negative for Glypican. Diffuse sinusoidal CD34 staining is present. Ki-67 proliferative index is approximately 2%. These changes did not permit a confident diagnosis of hepatic adenoma or hepatocellular carcinoma. The case was sent for consultation by multiple institutions with a consensus diagnosis of well-differentiated hepatic lesion/neoplasm. A follow-up liver wedge resection shows a hepatic neoplasm with areas of loss of reticulin staining. Focal stromal invasion is present. The neoplastic cells are positive for HepPar-1, Arginase-1, glutamine synthetase and Glypican (patchy). Final diagnose was rendered as SH-HCC.

Conclusion

The diagnosis of SH-HCC requires high level of suspicion on a biopsy specimen, especially in a background of steatohepatitis. A reticulin stain and immunohistochemical stains may not be helpful. Clinical- radiological correlation should always be considered.